Production of optical pulses at a desired wavelength using solition self-frequency shift in higher-order-mode fiber

ABSTRACT

The present invention relates to an apparatus for producing optical pulses of a desired wavelength. The apparatus includes an optical pulse source operable to generate input optical pulses at a first wavelength. The apparatus further includes a higher-order-mode (HOM) fiber module operable to receive the input optical pulses at the first wavelength, and thereafter to produce output optical pulses at the desired wavelength by soliton self-frequency shift (SSFS). The present invention also relates to a method of producing optical pulses having a desired wavelength. This method includes generating input optical pulses using an optical pulse source, where the input optical pulses have a first wavelength and a first spatial mode. The input optical pulses are delivered into an HOM fiber module to alter the wavelength of the input optical pulses from the first wavelength to a desired wavelength by soliton self-frequency shift (SSFS) within the HOM fiber module, thereby producing output optical pulses having the desired wavelength.

FIELD OF THE INVENTION

The present invention relates to the production of optical pulses at adesired wavelength using soliton self-frequency shift inhigher-order-mode fibers.

BACKGROUND OF THE INVENTION

The phenomenon of soliton self-frequency shift (SSFS) in optical fiberin which Raman self-pumping continuously transfers energy from higher tolower frequencies (Dianov et al., JETP. Lett. 41:294 (1985)) has beenexploited over the last decade in order to fabricate widelyfrequency-tunable, femtosecond pulse sources with fiber delivery(Nishizawa et al., IEEE Photon. Technol. Lett. 11:325 (1999); Fermann etal., Opt. Lett. 24:1428 (1999); Liu et al., Opt. Lett. 26:358 (2001);Washburn et al., Electron. Lett. 37:1510 (2001); Lim et al., Electron.Lett. 40:1523 (2004); Luan et al., Opt. Express 12:835 (2004). Becauseanomalous (positive) dispersion (β₂<0 or D>0) is required for thegeneration and maintenance of solitons, early sources which made use ofSSFS for wavelength tuning were restricted to wavelength regimes >1300nm where conventional silica fibers exhibited positive dispersion(Nishizawa et al., IEEE Photon. Technol. Lett. 11:325 (1999); Fermann etal., Opt. Lett. 24:1428 (1999)). The recent development of index-guidedphotonic crystal fibers (PCF) and air-core photonic band-gap fibers(PBGF) relaxed this requirement with the ability to design largepositive waveguide dispersion and therefore large positive netdispersion in optical fibers at nearly any desired wavelength (Knight etal., IEEE Photon. Technol. Lett. 12:807 (2000)). This allowed for anumber of demonstrations of tunable SSFS sources supporting inputwavelengths as low as 800 nm in the anomalous dispersion regime (Liu etal., Opt. Lett. 26:358 (2001); Washburn et al., Electron. Lett. 37:1510(2001); Lim et al., Electron. Lett. 40:1523 (2004); Luan et al., Opt.Express 12:835 (2004)).

Unfortunately, the pulse energy required to support stable Raman-shiftedsolitons below 1300 nm in index-guided PCFs and air-core PBGFs is eitheron the very low side, a fraction of a nJ for silica-core PCFs, (Washburnet al., Electron. Lett. 37:1510 (2001); Lim et al., Electron. Lett.40:1523 (2004)) or on the very high side, greater than 100 nJ (requiringan input from an amplified optical system) for air-core PBGFs (Luan etal., Opt. Express 12:835 (2004)). The low-energy limit is due to highnonlinearity in the PCF. In order to generate large positive waveguidedispersion to overcome the negative dispersion of the material, theeffective area of the fiber core must be reduced. For positive totaldispersion at wavelengths <1300 nm this corresponds to an effectivearea, A_(eff), of 2-5 μm², approximately an order of magnitude less thanconventional single mode fiber (SMF). The high-energy limit is due tolow nonlinearity in the air-core PBGF where the nonlinear index, n₂, ofair is roughly 1000 times less than that of silica. These extreme endsof nonlinearity dictate the required pulse energy (U) for solitonpropagation, which scales as UD·A_(eff)/n₂. In fact, most microstructurefibers and tapered fibers with positive dispersion are intentionallydesigned to demonstrate nonlinear optical effects at the lowest possiblepulse energy, while air-core PBGFs are often used for applications thatrequire linear propagation, such as pulse delivery. For these reasons,previous work using SSFS below 1300 nm were performed at solitonenergies either too low or too high (by at least an order of magnitude)for many practical applications, such as multiphoton imaging where bulksolid state lasers are currently the mainstay for the excitation source(Diaspro, A., Confocal and Two-Photon Microscopy, Wiley-Liss:New York(2002)).

Applications of Femtosecond Sources in Biomedical Research.

There are a number of biomedical applications that require femtosecondsources. Although applications requiring a large spectral bandwidth(such as optical coherence tomography) can also be performed usingincoherent sources such as superluminescent diodes, techniques based onnonlinear optical effects, such as multiphoton microscopy and endoscopy,almost universally require the high peak power generated by afemtosecond source.

Molecular two-photon excitation (2PE) was theoretically predicted byMaria Goppert-Mayer in 1931 [1]. The first experimental demonstration oftwo-photon absorption [2], however, came nearly 30 years later, afterthe technological breakthrough of the invention of the ruby laser in1960. It was almost another 30 years before the practical application of2PE for biological imaging was demonstrated at Cornell University in1990 [3]. Once again, this new development was propelled in large partby the rapid technological advances in mode-locked femtosecond lasers[4, 5]. Since then, two-photon laser scanning microscopy has beenincreasingly applied to cell biology and neurosciences [6-10]. A numberof variations, including three-photon excitation (3PE) [1-14], secondand third harmonic generation imaging [15-17], near-field enhancedmultiphoton excitation [18] and multiphoton endoscopic imaging [19],have emerged and further broadened the field, which is currently knownas multiphoton microscopy (MPM). Today, MPM is an indispensable tool inbiological imaging. Like any nonlinear process, however, multiphotonexcitation requires high peak intensities, typically 0.1 to 1 TW/cm²(TW=10¹² W). Besides tight spatial focusing, MPM typically requirespulsed excitation sources to provide additional temporal “focusing” sothat efficient multiphoton excitation can be obtained at low averagepower. For example, a femtosecond laser with 100-fs pulse width (τ) at100 MHz pulse repetition rate (f) will enhance the excitationprobability of 2PE by a factor of 10⁵, i.e., the inverse of the dutycycle (fτ). The development of multiphoton imaging depends critically onultrafast technologies, particularly pulsed excitation source.

Endoscopes play an important role in medical diagnostics by making itpossible to visualize tissue at remote internal sites in a minimallyinvasive fashion [20]. The most common form employs an imaging fiberbundle to provide high quality white light reflection imaging. Laserscanning confocal reflection and fluorescence endoscopes also exist [21,22] and can provide 3D cellular resolution in tissues. Confocalendoscopes are now becoming available commercially (Optiscan Ltd,Australia, Lucid Inc, Rochester) and are being applied in a number ofclinical trials for cancer diagnosis. Multiphoton excitation basedendoscopes has attracted significant attention recently. There were anumber of advances [23], including fiber delivery of excitation pulses[24], miniature scanners [25], double clad fibers for efficient signalcollections [26], etc. Thus, just like MPM has proven to be a powerfultool in biological imaging, multiphoton endoscopes have great potentialsto improve the capability of the existing laser-scanning opticalendoscopes. It is quite obvious that a compact, fully electronicallycontrolled, femtosecond system seamlessly integrated with fiber opticdelivery is essential for multiphoton endoscopy in medical diagnostics,particularly to biomedical experts who are not trained in lasers andoptics.

Perhaps the most promising and successful area in biomedical imagingthat showcases the unique advantage of multiphoton excitation is imagingdeep into scattering tissues [10]. In the past 5 to 10 years, MPM hasgreatly improved the penetration depth of optical imaging and proven tobe well suited for a variety of imaging applications deep within intactor semi-intact tissues, such as demonstrated in the studies of neuronalactivity and anatomy [27], developing embryos [28], and tissuemorphology and pathology [29]. When compared to one-photon confocalmicroscopy, a factor of 2 to 3 improvement in penetration depth isobtained in MPM. Nonetheless, despite the heroic effort of employingenergetic pulses (˜μJ/pulse) produced by a regenerative amplifier [30],MPM has so far been restricted to less than 1 mm in penetration depth.One promising direction for imaging deep into scattering tissue is touse longer excitation wavelength. Although the “diagnostic andtherapeutic window,” which is in between the absorption regions of theintrinsic molecules and water, extends all the way to ˜1300 nm (seewater absorption spectrum in FIG. 4), previous investigations involvingmultiphoton imaging are almost exclusively carried out within the nearIR spectral window of ˜0.7 to 1.1 μm, constrained mostly by theavailability of the excitation source. Currently, there are only twofemtosecond sources at the spectral window of 1200 to 1300 nm, theCr:Forstcritc laser and the optical parametric oscillator (OPO) pumpedby a femtosecond Ti:Sapphirc (Ti:S) laser. In terms of robustness andeasy operation, both sources rank significantly below the Ti:S laser.Thus, the development of a reliable fiber source tunable from 1030 to1280 nm will open up new opportunities for biomedical imaging,particularly for applications requiring deep tissue penetration.

Femtosecond Sources for Multiphoton Imaging.

Shortly after the inception of MPM, mode-locked solid state femtosecondlasers, most commonly the Ti:S lasers [5, 31], have emerged as thefavorite excitation sources to dominate the MPM field today. Whencompared to earlier ultrafast lasers, e.g., ultrafast dye lasers, theTi:S lasers are highly robust and flexible. The concurrent developmentof the mode-locked Ti:S lasers was perhaps the biggest gift for MPM andenabled MPM to rapidly become a valuable instrument for biologicalresearch. Nonetheless, the cost, complexity, and the limited potentialfor integration of the hulk solid state lasers have hampered thewidespread applications of MPM in biological research. The fact that adisproportionate number of MPM systems are located in physics andengineering departments [32], instead of the more biologically orientedinstitutions, reflects at least in part the practical limitations of thefemtosecond pulsed source. Obviously, the requirement of a robust, fiberdelivered, and cheap source is even more urgent for multiphotonendoscopy in a clinical environment.

Mode-locked femtosecond fiber lasers at 1.03 and 1.55 μm [33, 34] havebeen improving significantly in the last several years, mainly in theoutput pulse energy (from 1 to ˜10 nJ) [35]. Even higher pulse energycan be achieved in femtosecond fiber sources based on fiber chirpedpulse amplification [36]. However, femtosecond fiber sources, includinglasers and CPA systems, have seen only limited applications inmultiphoton imaging. The main reason is that they offer very limitedwavelength tunability (tens of nanometer at best), severely restrictingthe applicability of these lasers, making them only suitable for somespecial purposes. In addition, existing femtosecond fiber sources athigh pulse energy (>1 nJ) are not truly “all fiber,” i.e., the outputare not delivered through a single mode optical fiber. Thus, additionalsetup, typically involving free-space optics, must be used to deliverthe pulses to the imaging apparatus, partially negating the advantagesof the fiber source. Reports have demonstrated the possibility ofpropagating femtosecond IR pulses through a large core optical fiber atintensities high enough (˜1 nJ) for multiphoton imaging [24]. Inaddition, a special HOM fiber that is capable of delivery energeticfemtosecond pulses (˜1 nJ) has been demonstrated [37]. However, bothfibers have normal dispersion, and both require a free-space gratingpair for dispersion compensation. Not only is such a grating pair lossyand complicated to align, it needs careful adjustment for varying fiberlength, output wavelength, and output pulse energy, and falls short ofthe requirement for most biomedical research labs and future clinicalapplications.

The present invention is directed to overcoming these and otherdeficiencies in the art.

SUMMARY OF THE INVENTION

The present invention relates to an apparatus for producing opticalpulses of a desired wavelength. The apparatus includes an optical pulsesource operable to generate input optical pulses at a first wavelength.The apparatus further includes a higher-order-mode (HOM) fiber moduleoperable to receive the input optical pulses at the first wavelength,and thereafter to produce output optical pulses at the desiredwavelength by soliton self-frequency shift (SSFS).

The present invention also relates to a method of producing opticalpulses having a desired wavelength. This method includes generatinginput optical pulses using an optical pulse source, where the inputoptical pulses have a first wavelength and a first spatial mode. Theinput optical pulses are delivered into an HOM fiber module to alter thewavelength of the input optical pulses from the first wavelength to adesired wavelength by soliton self-frequency shift (SSFS) within the HOMfiber module, thereby producing output optical pulses having the desiredwavelength.

The present invention is useful in providing optical pulses that atunable over a wide wavelength range. The present invention can be usedin any application that involves optical pulses. Examples of such usesinclude, without limitation, spectroscopy, endoscopy, and microscopyapplications. Such uses can involve medical, diagnostic, and non-medicalapplications. In one embodiment, the present invention provideswavelength tunable, all-fiber, energetic femtosecond sources. In anotherembodiment, the present invention provides femtosecond sources based ona new class of optical fiber (i.e., an HOM fiber) that was recentlydemonstrated, where, for the first time, a large anomalous dispersionwas achieved at wavelengths below 1300 nm in an all-silica fiber.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A: Total dispersion for propagation in the LP₀₂ mode. FIG. 1B:Experimental near-field image of the LP₀₂ mode with effective areaAeff=44 μm². FIG. 1C: Experimental setup used to couple light throughthe HOM fiber module.

FIG. 2A: Soliton self-frequency shifted spectra corresponding todifferent input pulse energies into the HOM fiber. All traces taken at4.0 nm resolution bandwidth (RBW). Input pulse energy noted on eachtrace. Power conversion efficiency is 57% for 1.39 nJ input. FIG. 2B:High resolution trace of the initial spectrum; 0.1 nm RBW. FIG. 2C: Highresolution trace of the shifted soliton for 1.63 nJ input into the HOM;0.1 nm RBW. FIG. 2D: Soliton self-frequency shifted spectra calculatedfrom simulation using a 200 fs input Gaussian pulse and shifted solitonenergies comparable to those in FIG. 2A. Input pulse energy noted oneach trace.

FIG. 3. Second-order interferometric autocorrelation trace of HOM outputfor 1.39 nJ input pulses. Autocorrelation FWHM measured to be 92 fscorresponding to a deconvolved pulse width of 49 fs.

FIG. 4 shows an absorption coefficient of water as a function ofwavelength. The arrows indicate the tuning ranges of a femtosecond Ti:Slaser, a Ti:S laser pumped OPO, and the proposed sources. The solidcircles represent the wavelength of existing femtosecond fiber lasers.The tuning range that has already been demonstrated in a preliminarystudy is also indicated.

FIG. 5 is a schematic drawing of one embodiment of an all fiber,wavelength tunable, energetic, femtosecond source.

FIG. 6A is an output spectrum and FIG. 6B is a second-orderautocorrelation measurement of the pulse width (˜300 fs) of a commercialfiber source (Uranus 001, PolarOnyx Inc.). The output pulse energy ofthe source is 14.9 nJ, and the repetition rate is 42 MHz. FIG. 6C is aphotograph of the fiber source. The lateral dimension of the source isabout one foot. Data and photograph courtesy of PolarOnyx Inc.

FIG. 7 shows an output of self-similar laser. Left: theoreticalspectrum, output pulse, and equi-intensity contours of the pulse as ittraverses the laser. Right: experimental spectrum (on logarithmic andlinear scales), and measured autocorrelations of the pulse directly fromthe laser (red, broad pulse) and after dechirping (blue, short pulse).

FIG. 8 shows a comparison of modal behaviour between conventional LP01(SMF, top-schematic) and LP02 (bottom-simulated) modes. FIG. 8A:Near-field images. FIG. 8B: Mode profiles at various wavelengths.Conventional mode transitions from high to low index; designed HOM showsopposite evolution. Grey background denotes index profile of the fiber.FIG. 8C: Resultant total dispersion (D_(total), solid). Also shown aresilica material dispersion (D_(m), dashed) and zero-dispersion line(dotted). Arrows show contribution of waveguide dispersion (D_(w)) tototal dispersion.

FIG. 9A is an index profile of the HOM fiber and FIG. 9B experimentallymeasured near-field image LP02 mode with A_(eff)˜44 μm². FIG. 9C:Schematic of the HOM fiber module—in/output LPGs ensure device iscompatible with conventional single mode fibers. FIG. 9D: Devicetransmission: 51-nm bandwidth and 2% total insertion loss at 1080 nm.FIG. 9E: Comparison of the dispersions of the HOM fiber (solid) and theconventional SMF (dashed). Also shown is the zero-dispersion line(dotted).

FIG. 10 is a demonstration of SSFS in a tapered PCF (inset in b). (a)Output spectra at different values of output soliton power. (b) Measuredwavelength shift vs. input power.

FIG. 11 shows results of SSFS in a PCF. A pulse at 1.03 μm is shifted tobeyond 1.3 μm in this example. Result of numerical simulation is shownfor comparison.

FIG. 12 is a photo of the HOM fiber module for the demonstration ofSSFS. The splice protector also protects the in-fiber LPG modeconverter.

FIG. 13( a) Soliton self-frequency shifted spectra corresponding todifferent input pulse energies into the HOM fiber module. (b) Highresolution trace of the initial input spectrum over a 30-nm span. (c)High resolution trace over a 100-nm span of the shifted soliton for1.63-nJ input into the HOM fiber. (d) Solution self-frequency shiftedspectra calculated from simulation using a 280-fs Gaussian pulse inputand at shifted soliton energies comparable to those in (c). (c) Measuredsecond-order interferometric autocorrelation trace of the output solitonat 1.39-nJ pulse input into the HOM fiber, corresponding to adeconvolved pulse width of approximately 50 fs (FWHM). The tall spike inthe experimental spectra (a) is entirely due to the imperfection of ourcommercial fiber source, where a CW-like spike was present at 1064 nm(b).

FIG. 14 shows designed dispersion (D) vs. wavelength curves. (a) forwavelength tuning at 775-nm input. (b) for wavelength tuning at 1030-nminput. The calculated wavelength tuning range is indicated. The existingHOM fiber (solid line in b) is also indicated.

FIG. 15 shows output spectra (a) at various input pulse energies for a1-meter HOM fiber and (b) at various propagation distance (z) in the HOMfiber (i.e., HOM fiber length) for an input pulse energy of 2.5 nJ. Forcomparison, the input spectrum is also shown. We have offsetted eachspectrum vertically so that all can be displayed on the same plot.

FIG. 16 shows two-photon excitation spectra of fluorophores. Datarepresent two-photon action cross section, i.e., the product of thefluorescence emission quantum efficiencies and the two-photon absorptioncross sections. 1 GM=10⁻⁵⁰ cm⁴ s/photon. Spectra are excited withlinearly polarized light using a Ti:S pumped OPO (Spectra physics). Alldyes are from Molecular Probe.

FIG. 17 is a temporal pulse evolution in an HOM fiber module at variouspropagation distance (z) with a 2.6-nJ chirped input pulse. Insert in(d) is the zoom-in version of the soliton pulse. The FWHM of the solitonis 44 fs.

FIG. 18 shows energy of self-similar pulses (up-triangles, red line)obtained in numerical simulations of fiber laser, plotted versus netcavity dispersion. The down-triangles and blue line are the energiesproduced by stretched-pulse operation of the laser.

FIG. 19 (a) General HOM fiber design (i.e., index vs. radial position)for attaining anomalous waveguide dispersion. (b) Simulated total D vs.wavelength curves for a variety of profiles. The material dispersion ofsilica (dashed line) is also shown.

FIG. 20 shows Index vs. radial position of the designed and fabricatedfiber measured at several perform positions. Lengthwise uniformity ofthe perform ensures similar properties over km lengths of this fiber.

FIG. 21 is a schematic drawing of the proposed all fiber, wavelengthtunable, energetic, femtosecond source after full system integration.The dashed boxes indicate the components developed in Aims 1 and 2. ACPA approach for the fixed wavelength fiber source is shown. SHG isneeded only for the 775-nm input. The fiber lengths of the chirpingfiber and the HOM fiber are approximate. The dark dots indicatelocations for fiber splicing. The cross (x) indicates location for fibersplicing in power tuning, or connectorization in length or sequentialtuning with multiple HOM fiber modules. The mode profiles of thefundamental and LP02 modes are also shown.

FIG. 22 shows an instrument for multiphoton spectroscopy on cancertissues. The inset shows a schematic contour plot of theexcitation-emission matrix (EEM).

FIG. 23 shows a two-photon excitation spectra (A) and emission spectra(B) of CFP and monomeric eGFP, two common genetically encodablefluorescent proteins. A system capable of switching the excitationwavelength of ms timescales (i.e. between forward and return scan lines)would be able to more cleanly separate the emissions.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to an apparatus for producing opticalpulses of a desired wavelength. The apparatus includes an optical pulsesource operable to generate input optical pulses at a first wavelength.The apparatus further includes a higher-order-mode (IIOM) fiber moduleoperable to receive the input optical pulses at the first wavelength,and thereafter to produce output optical pulses at the desiredwavelength by soliton self-frequency shift (SSFS).

In one embodiment, the HOM fiber module includes an HOM fiber. SuitableHOM fibers can include, without limitation, a solid silica-based fiber.In another embodiment, the HOM fiber module includes an HOM fiber and atleast one mode converter. The at least one mode converter can beconnectedly disposed between the optical pulse source and the HOM fiber.The HOM fiber module can also include an HOM fiber, a mode converterconnectedly disposed between the optical pulse source and the HOM fiber,and also a second mode converter terminally connected to the HOM fiber.Suitable mode converters that can be used in the present invention arewell known in the art, and can include, for example, a long periodgrating (LPG).

Suitable optical pulse sources that can be used in the present inventioncan include, without limitation, mode-locked lasers and chirped pulseamplification (CPA) systems. More particularly, the mode-locked lasercan be a mode-locked fiber laser, and the CPA system can be a fiber CPAsystem. The optical pulse source used in the present invention caninclude those that generate input optical pulses having various pulseenergies. In one embodiment, the optical pulse source generates a pulseenergy of at least 1.0 nanojoules (nJ). In another embodiment, theoptical pulse source generates input optical pulses having a pulseenergy of between about 1.0 nJ and about 100 nJ.

The optical pulse source can also be one that generates input opticalpulses such that the first wavelength is a wavelength within thetransparent region of a silica-based fiber. In one embodiment, theoptical pulse source is one that generates a first wavelength below 1300nanometers (nm). In another embodiment, the optical pulse source is onethat generates a first wavelength between the range of about 300 nm andabout 1300 nm.

The optical pulse source used in the present invention can also be onethat generates input optical pulses having a subpicosecond pulse width.

Suitable HOM fiber modules that can be used in the present invention caninclude, without limitation, HOM fiber modules that produce outputoptical pulses having a pulse energy of at least 1.0 nJ. Suitable HOMfiber modules can also be those that produce output optical pulses suchthat the desired wavelength is a wavelength within the transparentregion of a silica-based fiber. In one embodiment, the HOM fiber moduleproduces an output optical pulse having a desired wavelength that isbelow 1300 nm. In another embodiment, the HOM fiber module produces anoutput optical pulse having a desired wavelength between the range ofabout 300 nm and about 1300 nm. The HOM fiber module can also be suchthat it produces output optical pulses having a subpicosecond pulsewidth.

The apparatus of the present invention can further include a powercontrol system connectedly disposed between the optical pulse source andthe HOM fiber module. The power control system for use in the presentinvention can be one that achieves subnanosecond power tuning of thefirst wavelength. Suitable power control systems can include, withoutlimitation, a lithium niobate (LiNbO₃) intensity modulator device.

The apparatus of the present invention can further include a single-modefiber (SMF) connectedly disposed between the optical pulse source andthe HOM fiber module.

The apparatus of the present invention can be used in a variety ofapplications where optical pulses of a desired wavelength are needed.For example, the apparatus can be effective in producing output opticalpulses that can penetrate animal or plant tissue at a penetration depthof at least 0.1 millimeters (mm).

The apparatus of the present invention can further be such that the HOMfiber module is terminally associated with medical diagnostic tools suchas an endoscope or an optical biopsy needle.

The apparatus of the present invention can further be functionallyassociated with a multiphoton microscope system.

The apparatus of the present invention can also further be functionallyassociated with a multiphoton imaging system.

The present invention also relates to a method of producing opticalpulses having a desired wavelength. This method includes generatinginput optical pulses using an optical pulse source, where the inputoptical pulses have a first wavelength and a first spatial mode. Theinput optical pulses are delivered into an HOM fiber module to alter thewavelength of the input optical pulses from the first wavelength to adesired wavelength by soliton self-frequency shift (SSFS) within the HOMfiber module, thereby producing output optical pulses having the desiredwavelength.

The method of the present invention can involve the use of the apparatusdescribed herein as well as the various aspects and components of theapparatus (e.g., the optical pulse source and the HOM fiber module)described herein.

In one embodiment, the method can further include converting the firstspatial mode of the input optical pulses into a second spatial modeprior delivering the input optical pulses into the HOM fiber so that theoutput optical pulses have the second spatial mode, where the firstspatial mode and the second spatial mode are different modes. Thismethod can further include reconverting the second spatial mode of theoutput optical pulses back to the first spatial mode.

In another embodiment, the method can further include tuning the firstwavelength of the input optical pulses to an intermediate wavelengthprior to delivering the input optical pulses into the HOM fiber. Thetuning can include, without limitation, power tuning. Such power tuningcan include varying the power of the input optical pulses so as to varythe desired wavelength. In one embodiment, the power tuning can includesubnanosecond power tuning using a power control system connectedlydisposed between the optical pulse source and the HOM fiber module.Suitable power control systems can include, without limitation, alithium niobate intensity modulator device. In another embodiment, thetuning can be achieved by varying the length of the HOM fiber so as tovary the desired wavelength.

Described in more detail below is the concept of SSFS in optical fibersand more particularly in HOM fibers.

Soliton Self-Frequency Shift (SSFS) in Optical Fibers.

SSFS is a well-known and well-understood phenomenon. The concept of SSFSwas first discovered ˜20 years ago in fiber optic communications, andmost of the past experiments on SSFS relates to telecom. Optical solitonpulses generally experience a continuous downshift of their carrierfrequencies when propagating in a fiber with anomalous dispersion. Thisso-called soliton self-frequency shift originates from the intra-pulsestimulated Raman scattering which transfers the short wavelength part ofthe pulse spectrum toward the long wavelength part [38] (SSFS sometimesis also called Raman soliton shift). Through the balancing of opticalnonlinearity and fiber dispersion (i.e., soliton condition), the pulsemaintains its temporal and spectral profiles as it shifts to the longerwavelengths. Although the physics of SSFS was well known for the last 20years, its practical application was limited because the use ofconventional fibers for generating wavelength-shifting solitons hasmajor limitations. However, several new classes of optical fibers, suchas photonic crystal fibers [39] (PCF, sometimes also known asmicrostructure fiber) and solid-core or air-core band gap fibers (BGF)[40], has generated enormous excitement in the last 5 years and greatlyimproved the feasibility of SSFS. Indeed, there are a number ofexperimental demonstrations of SSFS in PCF and BGF [41, 42, and 43].However, none of the previous work can generate soliton energies thatare of practical interest to biomedical research, i.e., solitons withpulse energies between 1 to 10 nJ and at wavelengths below 1300 nm. Aswe will elaborate below, the pulse energies produced in previous worksare either one to two orders of magnitude too small or several orders ofmagnitude too large.

Because material nonlinearity for silica glass is positive at therelevant spectral range, the fundamental condition to form an opticalsoliton in silica fiber is anomalous dispersion. In addition, theexistence of an optical soliton requires exact balance between fibernonlinearity and dispersion. Thus, the energy of an optical soliton(E_(s)) is determined by material nonlinearity and dispersion, andscales as [44]

E_(s)∝λ³·D·A_(eff)/n₂τ.  (1),

where n₂ is the nonlinear refractive index of the material, τ is thepulse width, D is the dispersion parameter, A_(eff) is the effectivemode field area, and λ is the wavelength. Although standard single modefibers (SMF) cannot achieve anomalous dispersion at λ<1280 nm, it wasrealized that the total dispersion (D) in a waveguide structure such asan optical fiber consists contributions from the material (D_(m)), thewaveguide (D_(w)), and the bandgap (in the case of BGF). Byappropriately engineering the contributions of the waveguide and/or thebandgap, it is possible to achieve anomalous dispersion (D>0) atvirtually any wavelength, thus, enabling soliton and SSFS at wavelengthsbelow 1280 nm. (It is worth noting that the dispersion parameter D isactually positive for anomalous dispersion.) Previously, there were twoapproaches to achieve anomalous dispersion, and therefore solitonpropagation and SSFS, at λ<1280 nm:

(1) Small-core PCF can achieve anomalous dispersion for wavelengths downto ˜550 nm [45]. When the waveguide is tightly confining, with theair-silica boundary defining the confinement layer, the waveguidedispersion (D_(w)) is akin to that of microwave waveguides withperfectly reflecting walls. Hence, large positive waveguide dispersionmay be realised by tightly-confined LP₀₁), (fundamental) modes in PCFs.However, the associated trade-off is with A_(eff), and designs thatyield dispersion >+50 ps/nm/km in the wavelength ranges of 800 nm or1030 nm typically have A_(eff) of 2-5 μm². Because the soliton energyscales with the value of D*A_(eff), a small A_(eff) will severely limitthe pulse energies that can be obtained with PCFs. For example, in oneexperiment using a special PCF structure performed, a soliton pulseenergy of ˜20 pJ was obtained at 800 nm [46], orders of magnitudesmaller than practical for imaging. Indeed, most PCF structures aredesigned to demonstrate nonlinear optical effects at the lowest possiblepulse energy.

(2) Air-guided BGFs potentially can offer anomalous dispersion at anywavelength [47], but the extremely low nonlinearities in these fibers(the nonlinearity of air is ˜one thousand times smaller than silicaglass) make them impractical for a device that utilises a nonlinearinteraction to achieve the frequency shift. In one demonstration, a MW(˜μJ pulse) optical amplifier is needed for observing SSFS inair-guiding fiber [43]. Not only is such a high power unnecessary formost biomedical applications, the cost and complexity of the high poweramplifier also makes it completely impractical as a tool for biomedicalresearch.

Although SSFS provides a convenient mechanism for wavelength tuning of afixed wavelength fiber laser, previous works in SSFS were performed atsoliton energies either too low or too high (by at least an order ofmagnitude) for practical use. Thus, it is essential to invent a newfiber structure, with just the right amount of optical nonlinearity anddispersion (i.e., D·A_(eff)/n₂) in order to produce soliton pulses ofpractical utility for biomedical imaging.

HOM Fiber.

An optical fiber generally propagates a number of spatial modes(electric field states). Because of modal dispersion and interference,however, only single mode fibers (i.e., fibers with only one propagatingmode) are of interest for applications such as high speed datatransmission and pulse delivery for imaging. It was realized, however, amultimode fiber can propagate only one mode if two conditions aremet: 1. the input field is a pure single mode and (2) the couplingsbetween various modes during propagation are small. In the case that theone propagating mode is not the fundamental mode, the fiber is called aHOM fiber. HOM fibers first attracted attention in opticalcommunications nearly ten years ago. The main motivation was fordispersion compensation of high bit-rate optical communications. Theadvantage of HOM fibers is to provide another degree of freedom in thedesign space to achieve the desired dispersion characteristics. Therewere a number of devices invented using HOM fibers [48]. In fact,dispersion compensators based on HOM fibers have been commerciallyavailable for several years [49].

We realized that the design freedoms enabled by HOM fibers are exactlywhat is needed for achieving the desired soliton energy at wavelengthbelow 1300 nm for biomedical imaging: (1) A higher order mode canachieve anomalous dispersion at wavelength below 1300 nm, a conditionnecessary for soliton and impossible to obtain in a conventional silicaSMF. (2) A higher order mode typically has a much larger A_(eff) thanthat of PCF for achieving higher soliton energy. (3) The silica core ofthe HOM fiber retains just enough nonlinearity to make SSFS feasible atpractical energy level. (4) The all silica HOM fiber retains the lowloss properties (for both transmission and bending) of a conventionalSMF, and allows easy termination and splicing. (5) A HOM fiber leveragesstandard silica fiber manufacturing platform, which has been perfectedover the course of 30 years with enormous resources. Thus, anappropriately designed HOM fiber can provide the necessarycharacteristics desired for biomedical imaging, and can be manufacturedimmediately with high reliability.

EXAMPLES

The Examples set forth below are for illustrative purposes only and arenot intended to limit, in any way, the scope of the present invention.

Example 1 Demonstration of Soliton Self-Frequency Shift Below 1300 nm inHigher-Order-Mode, Solid Silica-Based Fiber

Soliton-self frequency shift of more than 12% of the optical frequencywas demonstrated in a higher-order-mode (HOM) solid, silica-based fiberbelow 1300 nm. This new class of fiber shows great promise of supportingRaman-shifted solitons below 1300 nm in intermediate energy regimes of 1to 10 nJ that cannot be reached by index-guided photonic crystal fibersor air-core photonic band-gap fibers. By changing the input pulse energyof 200 fs pulses from 1.36 nJ to 1.63 nJ, clean Raman-shifted solitonswere observed between 1064 nm and 1200 nm with up to 57% powerconversion efficiency and compressed output pulse widths less than 50fs. Furthermore, due to the dispersion characteristics of the HOM fiber,red-shifted Cherenkov radiation in the normal dispersion regime forappropriately energetic input pulses were observed.

In this example, soliton self-frequency shift from 1064 nm to 1200 nmwith up to 57% power efficiency in a higher-order-mode (HOM) fiber isdemonstrated (Ramachandran et al., Opt. Lett. 31:2532 (2006), which ishereby incorporated by reference in its entirety). This new class offiber shows great promise for generating Raman solitons in intermediateenergy regimes of 1 to 10 nJ pulses that cannot be reached through theuse of PCFs and PBGFs. The HOM fiber used in the experiments of thisexample was shown to exhibit large positive dispersion (˜60 ps/nm-km)below 1300 nm while still maintaining a relatively large effective areaof 44 μm² (Ramachandran et al., Opt. Lett. 31:2532 (2006), which ishereby incorporated by reference in its entirety), ten times that ofindex-guided PCFs for similar dispersion characteristics. Throughsoliton shaping and higher-order soliton compression within the HOMfiber, clean 49 fs pulses from 200 fs input pulses were generated. Dueto the dispersion characteristics of the HOM fiber, red-shiftedCherenkov radiation in the normal dispersion regime for appropriatelyenergetic input pulses was also observed.

FIG. 1A shows the dispersion curve for the LP₀₂ mode in the HOM fiberused in the experiment of the present example. To generate positivedispersion below 1300 nm while simultaneously maintaining a largeeffective arca, light propagates solely in the LP₀₂ mode. Light iscoupled into the LP₀₂ mode using a low-loss long period grating (LPG)(Ramachandran, S., Journal of Lightwave Technology 23:3426 (2005), whichis hereby incorporated by reference in its entirety). The index profileof the HOM fiber is made such that the mode becomes more confined to thehigher-index core with an increase in wavelength, resulting in netpositive dispersion (Ramachandran et al., Opt. Lett. 31:2532 (2006),which is hereby incorporated by reference in its entirety). FIG. 1Ashows a dispersion of 62.8 ps/nm-km at 1060 nm which is comparable tothat of microstructured fibers used previously for SSFS (Liu et al.,Opt. Lett. 26:358 (2001); Washburn et al., Electron. Lett. 37:1510(2001); Lim et al., Electron. Lett. 40:1523 (2004), which are herebyincorporated by reference in their entirety), and exhibits two zerodispersion wavelengths at 908 nm and 1247 nm. The mode profile at theend face of the HOM fiber is shown in FIG. 1B, demonstrating a cleanhigher-order LP₀₂ mode and an effective area of 44 μm². A schematic ofthe fiber-module used for this experiment is shown in FIG. 1C. Herelight propagates in the fundamental mode through 12.5 cm of standardsingle mode (flexcore) fiber before being coupled into 1.0 m of the HOMfiber with a 2.5 cm LPG (entirely contained within a fiberfusion-splicing sleeve). Light resides in the LP₀₁ mode forapproximately half the length of the grating after which more than 99%is coupled into the LP₀₂ mode. The entire module has a total loss of0.14 dB which includes all splices, fiber loss, and mode conversion. Itis also noted that the all-silica HOM fiber leverages the standardsilica fiber manufacturing platform and retains the low loss properties(for both transmission and bending) of a conventional SMF, allowing easytermination and splicing.

The experimental setup is shown in FIG. 1C. The pump source consisted ofa fiber laser (Fianium FP1060-1S) which delivered a free space output of˜200 fs pulses at a center wavelength of 1064 nm and an 80 MHzrepetition rate. A maximum power of 130 mW was able to be coupled intothe fiber module corresponding to 1.63 nJ input pulses. Using a variableattenuator, the input pulse energy was varied from 1.36 nJ to 1.63 nJ toobtain clean spectrally-shifted solitons with a maximum wavelength shiftof 136 nm (12% of the carrier wavelength), FIG. 2A. Theoretical tracesfrom numerical simulation for similar input pulse energy are plottedadjacent to the experimental data in FIG. 2D. The split-step Fouriermethod was used in the simulation and included self-phase modulation(SPM), stimulated Raman scattering (SRS), self-steepening, anddispersion up to fifth-order. The dispersion coefficients were obtainedby numerically fitting the experimental curve in FIG. 1A and a nonlinearparameter γ=2.2 W⁻¹Km⁻¹ and a Raman response of T_(R)=5 fs were used(Agrawal, G. P., Nonlinear Fiber Optics, Third ed., Academic Press:SanDiego (2001), which is hereby incorporated by reference in itsentirety). The irregularly shaped spectrum of the input source was alsoapproximated (FIG. 1B) with an 8.5 nm, Gaussian shape corresponding to200 fs Gaussian pulses. Though a more accurate description shouldinclude the full integral form of the nonlinear Schrödinger equation(Agrawal, G. P., Nonlinear Fiber Optics, Third ed., Academic Press:SanDiego (2001), which is hereby incorporated by reference in itsentirety), the excellent qualitative match and reasonable quantitativematch validates this approach.

57% power conversion from the input pulse spectrum to the red-shiftedsoliton was measured for the case of 1.39 nJ input pulses to achieve˜0.8 nJ output soliton pulses, FIG. 2A. The corresponding second-orderinterferometric autocorrelation (FIG. 3) gives an output pulse width of49 fs, assuming a sech pulse shape (Nishizawa et al., IEEE Photon.Technol. Lett. 11:325 (1999), which is hereby incorporated by referencein its entirety), showing a factor of four in pulse width reduction dueto higher-order soliton compression (soliton order N=2.1) in the HOMfiber. The measured spectral bandwidth of 35 nm gives a time-bandwidthproduct of 0.386 which is 23% beyond that expected for a sech² pulseshape. It is believed that the discrepancy is likely due to dispersionfrom ˜5 cm of glass (collimating and focusing lenses) between the fiberoutput and the two-photon detector inside the autocorrelator. Thisexplanation is supported by numerical simulation which gives an outputpulse width of 40 fs. Of further note is the ripple-free,high-resolution spectrum of the shifted soliton for 1.63 nJ input, FIG.2C. This is indicative of propagation exclusively in the LP₀₂ mode sincemultimode propagation would surface as spectral interference.

Finally, the appearance of Cherenkov radiation centered about 1350 nmfor 1.45 nJ and 1.63 nJ input pulse energies, FIG. 2A. Here, as has beendemonstrated previously in PCF's (Skryabin et al., Science 301:1705(2003), which is hereby incorporated by reference in its entirety),Cherenkov radiation is generated from phase matching between the solitonand resonant dispersive waves. This process occurs most efficiently whenthe soliton approaches the zero dispersion wavelength where thedispersion slope is negative. Pumping more energy into the fiber doesnot red-shift the soliton any further, but instead transfers the energyinto the Cherenkov spectrum. As the input pulse energy is increased from1.45 nJ to 1.63 nJ (FIG. 2A), the soliton is still locked at a centerwavelength of ˜1200 nm but more energy appears in the Cherenkovspectrum. Simulations suggest that an ultrashort pulse can be filteredand compressed from this radiation to achieve energetic pulses acrossthe zero-dispersion wavelength.

Though not demonstrated in this example, light can be easily coupledback into the fundamental mode using another LPG at the output end.Previous work showed that by using a dispersion-matching design,ultra-large bandwidths can be supported by a LPG (Ramachandran, S.,Journal of Lightwave Technology 23:3426 (2005), which is herebyincorporated by reference in its entirety). Recently, conversionefficiency of 90% over a bandwidth of 200 nm was obtained for a similarfiber structure (Ramachandran et al., Opt. Lett. 31:1797 (2006), whichis hereby incorporated by reference in its entirety). Such a LPG willensure the output pulse is always converted back to a Gaussian profile,within the tuning range. An important consideration for the output LPGis its length. Since the energetic output pulses are solitons for aspecific combination of dispersion and A_(eff) of the L₀₂ mode,nonlinear distortions may occur when the energetic pulse goes to the(smaller A_(eff)) fundamental LP_(0l) mode at the output. However, thelength over which the signal travels in the LP₀₁ mode, and hence thedistortion it accumulates, can be minimized because the high-index coreof the HOM fibers enable LPG lengths of <5 mm. This implies that lightcan reside in the LP₀₁ mode for <2.5 mm, hence largely avoidingnonlinear distortions. Note that the requirement for short LPGs actuallycomplements the need for broad-bandwidth operation, since the conversionbandwidth is typically inversely proportional to the grating length(Ramachandran, S., Journal of Lightwave Technology 23:3426 (2005), whichis hereby incorporated by reference in its entirety).

Both the wavelength shift and pulse energy can be significantlyincreased beyond what has been demonstrated through engineering of thefiber module. For example, simple dimensional scaling of the indexprofile can be used to shift the dispersion curve of the LP₀₂ mode.Numerical modeling shows that an output soliton energy of approximately2 nJ can be realized if the dispersion curve is shifted ˜100 nm to thelonger wavelength side. Additionally, pulse energy can be scaled byincreasing D·A_(eff). Aside from increasing the magnitude of dispersionthrough manipulation of the index profile and dimensions of the fiber,the effective area can be significantly enhanced by coupling into evenhigher-order modes. An effective area of ˜2000 μm² (more than 40 timesthis HOM fiber) was recently achieved by coupling to the LP₀₇ mode(Ramachandran et al., Opt. Lett. 31:1797 (2006), which is herebyincorporated by reference in its entirety).

In summary, SSFS between 1064 nm and 1200 nm has been demonstrated in ahigher-order-mode, solid silica-based fiber. 49 fs Raman-shiftedsolitons were obtainable at 0.8 nJ with up to 57% power conversionefficiency. Due to the dispersion characteristics of the HOM fiber,Cherenkov radiation was also observed for appropriately energetic inputpulses. It is believed that HOM fiber should provide an ideal platformfor achieving soliton energies from 1 to 10 nJ for SSFS at wavelengthsbelow 1300 nm, filling the pulse energy gap between index-guided PCFsand air-core PBGFs. This intermediate pulse energy regime which couldnot be reached previously for SSFS could prove instrumental in therealization of tunable, compact, all-fiber, femtosecond sources for awide range of practical applications.

Example 2 All Fiber, Wavelength Tunable Femtosecond Sources forBiomedical Spectroscopy and Imaging

To emphasize the significance of the proposed femtosecond sources, wecompare our proposed sources with the existing mode-locked Ti:S laser,Ti:S pumped OPO and femtosecond fiber sources. FIG. 4 shows thewavelength tuning range of the sources. The absorption spectrum of wateris also shown to indicate the relevant wavelength range for biomedicalimaging. In essence, we want to develop two all-fiber femtosecondsources that cover approximately the same wavelength window as theexisting Ti:S laser and Ti:S pumped OPO. These wide wavelength tuningranges were simply impossible to achieve in any existing fiber sources,but are crucial to satisfy the requirements of nonlinear biomedicalimaging.

TABLE 1 Comparisons of femtosecond laser systems pulse energy (nJ)*pulse wavelength tuning size estimated free fiber width tuning rangespeed (cubic cost** fs lasers space delivered (fs) (nm) (s) feet) $kTi:S 25 5 ~60  700-1000 >10 ~10 170 Ti:S pumped 4 1 ~100 1120-1340 >10~14 250 OPO Cr:Forsterite 3 1 ~60 1230-1280 >10 ~4 68 Current 1030 15 5~200 1030-1070 >10 ~1 40 fiber source Current 1550 15 5 ~2001540-1590 >10 ~1 55 fiber source proposed 10 10 ~50  775-1000 ultrafast~1.5 70 source at 775 to 1000 proposed 10 10 ~50 1030-1280 ultrafast~1.5 50 source at 1030 to 1280 *The pulse energies listed are all at thepeak of the wavelength tuning range. **The estimated cost for theexisting laser systems are based on written price quotes from commercialvendors. The estimated cost for the proposed sources are largely basedon the price of existing sources at 1550 and 1030 nm, with our besteffort estimates for the additional cost of the HOM module and thecontrol electronics. We have also included necessary cost for frequencydoubling for the source at 775 nm.

Table 1 compares some of the key characteristics of the existing and ourproposed femtosecond sources. The proposed systems would be much lessexpensive than the currently used state-of-the-art single box Ti:Slasers (Spectra-Physics Mai Tai and the Coherent Chameleon), probably ⅓to ¼ the cost. The telecom manufacturing platform employed in theproposed fiber sources provides an inherent opportunity for further costreduction by volume scaling. In addition, there are the practicaladvantages offered by the all-fiber configuration, such as a compactfoot print and a robust operation. However, what truly sets the proposedfemtosecond sources apart from other existing fiber sources isperformance. Table 1 shows that the proposed all-fiber sources willachieve comparable or better performances in terms of output pulseenergy, pulse width, and wavelength tuning range when compared to bulksolid-state mode-locked lasers. We note that the output characteristicsof the proposed sources listed above are delivered through an opticalfiber. The elimination of the free-space optics makes the proposed fibersources more efficient in delivering power to an imaging setup. Thus,even at a slightly lower output power, the imaging capability of theproposed sources will likely be close to that of the free-space Ti:Slaser. It is worth emphasizing that significant research and developmentefforts have been devoted to femtosecond fiber sources in the last 15years or so. However, femtosecond fiber lasers have so far failed tohave a major impact in biomedical research. We believe the reason forthe low penetration of fiber femtosecond sources in the biomedical fieldis precisely due to various performance handicaps (such as pulse energy,wavelength tunability, pulse width, fiber delivery, etc.) that keptexisting fiber sources from being the “complete package.” It has nothingto do with the lack of demand or interest from biomedical researchers.Leveraging major technological advances in the fiber optic communicationfield and recent fiber laser developments, we believe we have finallyarrived at the stage where all-fiber femtosecond sources can be realizedwithout sacrificing performance. The successful completion of thisresearch program will make femtosecond sources truly widely accessibleto biologists and medical researchers and practitioner.

Preliminary Studies

This program explores a new route for generating energetic femtosecondpulses that are continuously tunable across a wide wavelength range,where, in contrast to previous approaches, ultrafast pulses arewavelength shifted in a novel HOM fiber module by SSFS. By eliminatingthe constraint of a broad gain medium to cover the entire tuning range,our approach allows rapid, electronically controlled wavelength tuningof energetic pulses in an all-fiber configuration. FIG. 5 schematicallyshows the design of the proposed excitation sources. We start off with asingle wavelength femtosecond fiber source at 1030 nm (or 775 nm withfrequency doubling from 1550 nm) with high pulse energy (10 to 25 nJ).The pulse is then propagated into a specifically designed HOM fibermodule for wavelength shifting via SSFS. The output wavelength of thesoliton pulses are controlled by the input pulse energies (and/or HOMfiber length). The target performances of the proposed systems are 5- to10-nJ pulses tunable from (1) 775 to 1000 nm and (2) 1030 to 1280 nm inan all-fiber configuration.

A feature of the proposed research is to harvest the recent developmentin femtosecond fiber sources and the latest breakthrough in fiber opticcommunication industry. During the course of our research anddevelopment in both academia and industry over the last 5 years, we haveaccumulated significant amount of preliminary data to support ourapproach. Specifically, we present below our studies on femtosecondfiber sources, HOM fibers, and SSFS, three key components of theproposed femtosecond source.

Preliminary Results on Femtosecond Fiber Sources.

The performance of fixed wavelength femtosecond fiber sources at 1030and 1550 nm have been improved significantly in the last several years.In fact, cost effective (˜$50 k) commercial fiber sources that arecapable of delivering ˜10-nJ pulse energies at 40 MHz repetition rate orhigher already exist. These sources are mostly based on fiber chirpedpulse amplification (CPA), where a low pulse energy oscillator serves asa seed source for the subsequent optical fiber amplifier. Examples ofsuch sources are offered by PolarOnyx Inc. and several other companies.FIG. 6 shows the output spectrum, pulse width (autocorrelation), and thephotograph of the device. These sources will be sufficient to achieveour first goals of 1- to 2-nJ output pulse after SSFS.

One of the draw backs of the commercial fiber sources is that theyemploy CPA technique to achieve the pulse energies required for ourapplication. The combination of oscillator and amplifier inevitablyincreases the cost of the system. Obviously, a lower cost approach willbe to build a fiber oscillator that can achieve the pulse energydirectly. A series of advances in femtosecond fiber lasers atwavelengths around 1 μm, based on ytterbium-doped fiber (Yb:fiber) havebeen reported. These include some of the best performances reported forfemtosecond fiber lasers [51, 52], such as the highest pulse energy (14nJ), highest peak power (100 kW), highest average power (300 mW) andhighest efficiency (45%). These are the first fiber lasers with pulseenergy and peak power comparable to those of solid-state lasers. Theselasers are diode-pumped through Fiber spliced to the gain fiber, and aretherefore already stable and reliable laboratory instruments.Uninterrupted operation for weeks at a time is routine, except when theperformance is pushed to the extremes of pulse energy or pulse duration.

The science that underlies the increases in pulse energy and peak powerlisted above is the demonstration of pulse propagation withoutwave-breaking [51]. The theoretical and experimental demonstration of“self-similar” evolution of short pulses in a laser [53] is a majorbreakthrough. This is a completely new way to operate a mode-lockedlaser. The laser supports frequency-swept (“chirped”) pulses that avoidwave-breaking despite having much higher energies than prior fiberlasers. The pulses can be dechirped to their Fourier-transform limit(FIG. 7, far-right panel), but the chirped output is actuallyadvantageous to the design of the proposed tunable source. Asillustrated by FIG. 7, the experimental performance of a self-similarlaser agrees with the theoretical spectral and temporal pulse shapes.This will allow us to use the theory to scale the pulse energy to whatis needed for the present project, as well as to design self-similarlasers at 1.55 μm based on erbium-doped fiber (Er:fiber). The maximumpulse energy reported from a femtosecond Er:fiber laser remains at ˜1 nJ[54], because there has been no attempt to develop self-similar lasersat 1.55 μm yet.

The high-energy lasers described above are experimental systems. Theyemploy some bulk optical components in the cavity, such as diffractiongratings for anomalous group-velocity dispersion. These componentsnaturally detract from the benefits of the fiber medium, and integratedversions of these devices will be needed for most applications.Virtually all of the components of the lasers are now available in fiberformat, and several advances toward the ultimate goal of all-fiber andenvironmentally-stable devices were made in the past few years. Thefirst step is to replace the diffraction gratings with a fiber device.Microstructure fibers, which have become commercially-available in thepast couple years, offer new combinations of dispersion andnonlinearity. The demonstration of dispersion control with a PCF [55]was the first such application of microstructure fibers. The resultinglaser is limited to low pulse energies by the small A_(eff) of the PCF.The extension of this approach to air-core PBF [47] is quite promising,as it will enable all-fiber lasers capable of wave-breaking-freeoperation.

Lasers with segments of ordinary fiber are susceptible to environmentalperturbations such as strain or temperature changes. For ultimatestability, it will be desirable to construct lasers withpolarization-maintaining fiber. We exploited the fact thatphotonic-bandgap fiber is effectively a polarization-maintaining fiberowing to the high index contrast, to build the firstenvironmentally-stable laser at 1 μm wavelength [56]. This laseroperates stably when the fiber is moved, twisted or heated. All thecomponents of the laser (which was a testbed for new concepts) now existin fiber format. It is therefore now possible to design lasers in whichthe light never leaves the fiber, and which are impervious toenvironmental perturbations.

Our development in robust femtosecond fiber lasers has already attractedsignificant commercial interests. PolarOnyx, Inc. (Sunnyvale, Calif.),and Clark/MXR, Inc. (Dexter, Mich.) have introduced products based onthe lasers described above (see FIG. 6 for the PolarOnyx source). Theappearance of commercial products two years after the initial reports ofnew concepts is evidence of the robust nature of the pulse-shaping inthe lasers.

Preliminary Results on HOM Fiber Modules.

Recently, an exciting new fiber type was demonstrated that yields stronganomalous dispersion in the 1-μm wavelength range, from an all-solidsilica fiber structure where the guidance mechanism is conventionalindex-guiding [57]. This represents a major breakthrough in fiber designbecause it was previously considered impossible to obtain anomalousdispersion at wavelength shorter than 1300 nm in such an all-silicafiber. The key to the design was the ability to achieve strong positive(anomalous) waveguide dispersion (D_(w)) for the LP₀₂ mode of aspecially designed HOM fiber. We demonstrated a fiber that had +60ps/nm-km dispersion for the LP₀₂ mode in the 1060-nm wavelength range.Combined with in-fiber gratings, this enabled constructing an anomalousdispersion element with low loss (˜1%), and an A_(eff) (44 μm²) that is10 times larger than PCF. Significantly, the guidance mechanism wasindex-guiding, as in conventional fibers. Hence, it retains thedesirable properties of conventional fibers, such as low-loss,bend-resistant, and lengthwise invariant (in loss, dispersion, etc),making them attractive for a variety of applications.

FIG. 8 provides an intuitive picture for the dispersive behaviour ofguided modes. FIG. 8A shows modal images for the fundamental LP₀₁ mode(top), and the higher order LP₀₂ (bottom) modes in a fiber. FIG. 8Bshows the evolution of these mode profiles as a function of wavelength.The LP₀₁ mode monotonically transitions from the high index central coreto the surrounding lower index regions. Thus, the fraction of powertravelling in lower index regions increases with wavelength increaseswith wavelength. Since the velocity of light increases as the index ofthe medium drops, the LP₀₁ mode experiences smaller group delays aswavelength increases. Waveguide dispersion (D_(w)), which is thederivative of group delay with respect to wavelength, is thus negativefor the LP₀₁ mode. In wavelength ranges in which material dispersion(D_(m)) is itself negative, the conventional LP₀₁ mode can achieve onlynegative dispersion values. This is illustrated in FIG. 8C (top), whichplots material as well as total dispersion of the LP₀₁ mode in the1060-nm wavelength range. Note that this discussion is for theconventional LP₀₁ mode in low-index-contrast all silica fiber that canbe realised by conventional fiber fabrication techniques. The LP₀₁ modecan in fact be designed to have large positive waveguide dispersion whenthe waveguide is tightly confining, such as in PCFs where the air-silicaboundary defines the confinement layer. Tight confinement, however,inevitably reduces A_(eff), making PCFs unsuitable for generatingenergetic soliton pulses.

In contrast, the LP₀₂ mode may be designed to have the mode evolutionshown in FIG. 8B (bottom). As the wavelength increases, the mode evolvesin the opposite direction, in that the mode transitions from the lowerindex regions to the higher index core. By the intuition described inthe previous paragraph, we infer that this mode will have D_(w)>0. Thisis illustrated in FIG. 8C (bottom), which shows that in the wavelengthrange where this transition occurs very large positive values of D_(w)are obtained, vastly exceeding the magnitude of (negative) D_(m). Thisyields a mode with positive total D (anomalous dispersion). Note thatthis evolution is governed by the “attractive” potential of various highindex regions of the waveguide, and can thus be modified to achieve avariety of dispersion magnitudes, slopes and bandwidths. This yields ageneralized recipe to obtain positive dispersion in a variety ofwavelength ranges. In fact, the enormously successful commercialdispersion compensation fiber was designed to achieve a variety ofdispersion values [58] based on the same concept.

FIG. 9A shows the index profile of the fiber we recently demonstratedthe broad, low index ring serves to substantially guide the LP₀₂ mode atshorter wavelengths, and the mode transitions to the small, high indexcore as wavelength increases (sec FIG. 8B for an example of this modeevolution). The experimentally recorded near-field image of this mode(FIG. 9B) reveals that it has an A_(eff)˜44 μm² at 1080 nm. FIG. 9Cshows the schematic of the module, depicting LPGs at the input andoutput of the fiber for mode conversion. The LPGs offer >90% conversionover a 51-nm bandwidth [48, 57] with peak coupling efficiencies of99.8%, yielding a 5-m HUM fiber module that has a 1-dB (˜23% loss)bandwidth of 51 nm (FIG. 9D). The transmission plot includes losscontributions of splices to SMF pigtails, and illustrates a device lossof only 2% at the center wavelength of 1080 nm. FIG. 9E shows thecentral parameter of interest—the dispersion of the LP_(O2) mode, asmeasured by spectral interferometry [59]. The dispersion is +60 ps/nm-kmat 1080 nm. The A_(eff) of this fiber (44 μm²) is an order of magnitudelarger than PCFs with similar dispersion (PCF A_(eff)˜4 μm²), and is infact larger than that of commercial SMFs at these wavelengths (SMFA_(eff)˜32 μm²).

Preliminary Results on SSFS.

There are a number of theoretical and experimental works on SSFS in thepast [60-64], including some targeting biomedical applications [65, 66].Reports have demonstrated SSFS in a number of fiber structures withinthe last 5 years. Previously, a novel tapered air-silica microstructurefiber was fabricated [41, 67] and demonstrated SSFS within the telecomwindow of 1.3 μm to 1.65 μm in a 10-cm long tapered microstructure fiber(inset in FIG. 10B). By varying the input power into the fiber, cleanself-frequency-shifted solitons were observed with a maximum wavelengthshift of ˜300 nm (FIG. 10A). Over 60% photons were converted to thefrequency-shifted soliton. The experimental dependence of solitonwavelength shift upon the incident power is shown in FIG. 10B. Similarexperiments were also demonstrated using a mode-locked fiber laser andPCF, shifting of the pulse wavelength continuously from 1 to 1.3 μm,with ˜1 m of photonic-crystal fiber (FIG. 11) [42]. Despite these earlyworks by ourselves and colleagues in the field, the highest solitonpulse energy of 0.1 to 0.4 nJ were obtained at 1030 to 1330 nm, stillsubstantially below 1 nJ.

Our recent breakthrough in the HOM fiber provides an exciting newopportunity for SSFS at the practical pulse energies of 1 to 10 nJ andat wavelength below 1300 nm. We have experimentally investigated thebehavior of SSFS at Cornell using the HOM fiber module provided by OFS.FIGS. 12 and 13 respectively show the experimental setup and results.Despite the fact that the HOM fiber module we used for the demonstrationwas designed for telecommunication purposes and was not ideally suitedfor SSFS at 1060-nm input, and the fact that the input pulse (inset inFIG. 13) from our commercial fiber source (Fianium, UK) is far fromperfect, our preliminary results unequivocally demonstrated thefeasibility and promise of the approach proposed. The key results aresummarized below:

1. A continuous wavelength shift of ˜130 nm (1060 to 1190) was achieved.

2. An output pulse energy of 0.84 nJ was obtained at 1.39-nJ inputpulse.

3. A high quality output pulse with ˜50-fs FWHM and a high conversionefficiency (i.e., the amount of optical power that is transferred to thewavelength shifted soliton) of ˜60% were obtained despite of the lowquality input pulse.

4. Remarkable agreement between experiments and numerical modeling wereachieved despite of the non-ideal input, demonstrating the robustness ofsoliton pulse shaping.

We note that at the highest input pulse energy, a new spectral peakappeared at much longer wavelength (˜1350 nm). This is the well-knownresonance Cerenkov radiation of the soliton due to the negativedispersion slope [68], which is also predicted by our simulation (FIG.13D). The onset of the Cerenkov radiation sets the long wavelength limitof the wavelength tuning range using SSFS and is highly predictable bythe zero dispersion wavelength of the fiber.

Preliminary Design Simulations.

Our initial success of SSFS in a HOM fiber module, and our provencapability to numerically predict the behavior of SSFS in a HOM fibergive us a high degree of confidence to achieve the stated goals. Throughextensive numerical simulations, we have already determined the requireddispersion (FIG. 14) and A_(eff) of the HOM fibers to achieve our firstgoal of 1- to 2-nJ pulses, tunable from 775 to 1000 nm and 1030 to 1280nm, FIG. 15A shows numerical simulation results of SSFS in such HOMfibers, by adjusting the launch power into the HOM fiber module. Theconversion efficiency is ˜70% for a Gaussian input pulse at 280-fs width(FWHM). Thus, even a 5-nJ pulse launched into the HOM fiber moduleshould be sufficient to achieve the design specifications. The outputpulse widths are between 50 and 70 fs throughout the tuning range. Verysimilar results were also obtained for the 775-nm input with the designcurve shown in FIG. 14A. We have further determined that a shift aslarge as ˜50 nm in zero-dispersion wavelength (the dash-dotted and thedotted line in FIG. 14B) will not significantly impact (<8% in outputpulse energy) the performance of the HOM fiber, making our designtolerant to fabrication imperfections. We note that the dispersioncurves shown in FIG. 14 are of the same functional dependence as ourexisting HOM module except that the peak wavelength is shifted foroptimum performance at 775-nm and 1030-nm input. Preliminary designsimulations indicated that such dispersion characteristics areachievable. In fact, dispersion characteristics better than those shownin FIG. 14 can be readily obtained. We emphasize that these preliminarydesign studies are based on highly reliable in-house design toolsdeveloped at OFS, and have taken into account practical considerationssuch as the manufacturability and yield of the fiber. Thus, thesedesigns are immediately viable commercially.

In addition to the power tuning of the output wavelength, an alternativemethod for wavelength tuning is simply using different fiber length.FIG. 15B shows the simulated output spectrum at various HOM fiberlengths while maintaining the input power. Tuning range identical tousing power adjustment, with a conversion efficiency of ˜70%, can beeasily achieved.

Preliminary Results of Multiphoton Imaging at Wavelength Beyond 1030 nm.

Perhaps the most promising and successful area in biomedical imagingthat showcases the unique advantage of multiphoton excitation is imagingdeep into scattering tissues. One of the promising approaches forimaging deep into scattering biological tissue is using longerexcitation wavelength. It is well known that the scattering mean freepath is proportional to the fourth power of the excitation wavelength inthe Rayleigh region, where the size of the scatterer (α) is much smallerthan the wavelength, i.e., 2πα/λ<0.1. When the size of the scattererbecomes comparable to the wavelength, i.e., in the Mie scatteringregion, the scattering mean free path (MFP) has a weaker dependence onthe wavelength. Nonetheless, the MFP increases with increasingexcitation wavelength. Although there is little data for tissuescattering beyond 1.1 μm, the available data at shorter wavelengthsclearly indicates the general trend that the scattering MFP increases asone uses longer excitation wavelength [69]. In fact, the “diagnostic andtherapeutic window,” which is in between the absorption regions of theintrinsic molecules and water, extends all the way to ˜1280 nm (see FIG.4 for the water absorption spectrum), significantly beyond the currentinvestigations of the near IR spectral window of ˜0.7 to 1.0 μm. Webelieve such a constrained is mostly caused by the lack of a convenientexcitation source.

There are a few experimental demonstrations of imaging at longerwavelengths by several groups [12, 70]. We have also carried outdetailed studies of multiphoton excitation of fluorophores within thespectral windows of 1150 to 1300 nm, and have found useful multiphotoncross sections (10 to 100 GM, comparable to fluorescein at shorterwavelength [71]) exist for a number of long wavelength dyes (FIG. 16).Clearly, longer wavelength imaging is feasible. In addition for thereduction of scattering of the excitation light, there are a number ofadditional advantages at the longer excitation window. It was shownpreviously that longer wavelength imaging is less damaging to livingtissues [72]. The use of longer excitation wavelengths will typicallyresult in longer wavelength fluorescence emissions and second or thirdharmonic generations. Because of the scattering and absorptionproperties of tissues, a long wavelength photon stands a much betterchance of being detected by the detector [73]. Thus, the long wavelengthwindow for multiphoton imaging should also improve the signalcollection, another critical issue in imaging scattering samples [74].There is no doubt that the creation of an all-fiber, wavelength tunable,energetic femtosecond source at the longer wavelength window of 1030 to1280 nm will open significant new opportunities for biomedical imaging.

Research Design and Methods.

Our overall approach to wavelength-tunable sources is to develop fibersources of 10- to 25-nJ and ˜300-fs pulses, which will propagate in HOMfiber modules as Raman solitons to produce the desired outputs. Startingwith pulses at 775 nm (1030 nm), pulses tunable from 775 to 1000 nm(1030 to 1280 nm) will be generated. The source development that wepropose is enabled by the coincident advances in short-pulse fiberlasers and propagation of higher-order modes, along with the commercialdevelopment of semiconductor structures for stabilizing short-pulselasers (to be described below). The availability of excellent fibers andcontinued improvement in the performance and cost of high-power laserdiodes provide the technical infrastructure needed to support thedevelopment of short-pulse fiber devices.

Aim 1: Single Wavelength all-Fiber Femtosecond Sources.

We will develop single wavelength all-fiber femtosecond sources at 1030nm and 775 nm with pulse energies at 10 and 25 nJ at repetition rates of40 to 100 MHz.

Our first step is to modify and optimize commercially availablefemtosecond fiber sources to achieve ˜10-nJ pulses, which will besufficient to achieve our first goal of 1- to 2-nJ output pulses.Although we are fully capable of building such sources ourselves, we aimto jump start the program by fully leveraging existing commercialtechnologies. The main task during this stage is to make the commercialsources truly all-fiber. We realized that one of the main drawbacks ofexisting commercial fiber sources is that they are not all-fiber. Forexample, the PolarOnyx system (FIG. 6) requires a separate gratingcompressor box (not shown in the photograph) to de-chirp the outputpulse at 14-nJ output. As we have discussed, free-space components suchas the grating compressor not only negate many advantages of the fibersource, they also make the fiber source ironically incompatible withfiber delivery.

Energetic femtosecond fiber sources (either from an oscillator or a CPAsystem) have typically chirped output to avoid optical nonlinearity, andtherefore, external dispersion compensation is required to recover thefemtosecond pulses. The main reason for the required free-space gratingcompressor in the current fiber source is the lack of low nonlinearityanomalous dispersion fiber, i.e., fibers with large A_(eff) and largepositive D value. Although airguided BGF can be used for dispersioncompensation, there were a number of practical issues such astermination, fusion splice, birefringence, loss, etc. On the other hand,the proposed HOM fiber can easily perform dispersion compensation inaddition to SSFS, by simply adding HOM fiber length in the HOM fibermodule. For example, with a typical chirp of 0.24 ps²/nm from a fibersource (the amount of chirp caused by ˜12 m of SMF at 1030 nm), oursimulation shows that a HOM fiber length of ˜6 m will produce the outputnearly identical to that shown in FIG. 15. FIG. 17 shows the pulseevolution through 1 meter of standard SMF pigtail and approximately 6meter of HOM fiber starting with a typical output chirp of 0.24 ps²/nm.Intuitively, the first ˜3 meters of the HOM fiber simply serves as adispersion compensator to compress the pulse. The pulse experiences bothdispersive and nonlinear compression in the next ˜2 meters of the HOMfiber, and the last meter or so of HOM fiber docs the SSFS. Because thetransmission loss of the HOM fiber is extremely low (similar toconventional SMF where light loses half of its power over a length of 10miles), HOM fiber length of tens of meters will incur essentially zeroloss. In fact, as we will explain in greater details in Aim 4, thelonger fiber length not only compensates pulse chirp from the fibersource, making the source all-fiber, it would simultaneously offer atremendous practical advantage in a clinical environment.

The second step, which involves our own laser and source development,aims to improve the pulse energy to ˜25 nJ in an all fiber design. Suchpulse energies are necessary for achieving a final tunable output of 5-to 10-nJ pulses. There are two approaches to achieve our aim.

The first approach closely follows the strategy of the existingcommercial devices using CPA. In a realistic fiber amplifier capable ofthe needed performance, a pulse is taken from an oscillator by splicingon an output fiber (tens of meters in length) where the pulse is highlystretched temporally. The stretched pulse is then amplified to highpulse energy by a fiber amplifier. Nonlinear effects that could distortthe pulse are avoided because the pulse is stretched, which reduces thepeak power. The output from the amplifier will be an amplified versionof the same chirped pulse. The pulse is contained in ordinarysingle-mode fiber throughout the device. The above described CPA schemehas enabled significantly improved pulse energy in fiber amplifiers.Even μJ pulse energies can be obtained (although at much lowerrepetition rate). For our proposed sources, we will amplify pulses to 25nJ at 1030. We aim to amplify to 50 nJ at 1550 nm in order to obtain˜25-nJ pulses at 775 nm. Commercial fiber amplifier modules alreadyexist to delivery the necessary power for our applications. In addition,methods for overcoming fiber nonlinearity in a fiber CPA system havebeen demonstrated [75, 76]. Thus, we do not anticipate any difficulty inachieving these design goals.

The combination of a laser and an amplifier in our first approach allowsboth to be designed easily, and is certain to meet or exceed our designspecifications. Indeed, it is highly likely that commercial femtosecondfiber sources based on the CPA technique can deliver the necessary pulseenergy (25 to 50 nJ) and power (1 to 2 watts) within the grant period.Thus, there is a possibility that we can continue leveraging commercialfemtosecond fiber sources. On the other hand, the addition of anamplifier adds cost and complexity to the source (at least one more pumplaser and driver will be required), and always adds noise to the output.Ultimately, it will be desirable to reach the needed pulse energiesdirectly from oscillators. Thus, as an alternative and lower costapproach, we will pursue the development of high-energy oscillators inparallel with the construction of low-energy oscillators that areamplified to the required energies.

Alternative Approach: Development of High-Energy Fiber Oscillators.

The essential physical processes in a femtosecond laser are nonlinearphase accumulation, group-velocity dispersion, and amplitude modulationproduced by a saturable absorber. A real or effective saturable absorberpreferentially transmits higher power, so it promotes the formation of apulse from noise, and sharpens the pulse. Once the pulse reaches thepicosecond range, group-velocity dispersion and nonlinearity determinethe pulse shape. In the steady state, the saturable absorber thus playsa lesser role, stabilizing the pulse formed by dispersion andnonlinearity. It is known that the pulse energy is always limited byexcessive nonlinearity. This limitation is manifested in one of twoways:

(1) A high-energy pulse accumulates a nonlinear phase shift that causesthe pulse to break into two (or more) pulses. This is referred to as“wave-breaking.”

(2) To date, the best saturable absorber for fiber lasers is nonlinearpolarization evolution (NPE), which produces fast and strong amplitudemodulation based on polarization rotation. It was employed in the Ybfiber lasers described in our preliminary results. A disadvantage of NPEis that the transmittance is roughly a sinusoidal function of pulseenergy; the transmittance reaches a maximum and then decreases withincreasing energy. Once the NPE process is driven beyond that maximumtransmittance, pulses are suppressed because lower powers experiencelower loss and are thus favored in the laser. This situation is referredto as “over-driving” the NPE.

Thus, eliminating “wavebreaking” and “over-driving” are essential inorder to achieve high pulse energy from a fiber laser. We have shownthat the first limitation, which is the more fundamental of the two, canbe avoided [51, 53] using self-similar pulse evolution. We havecalculated the energy of stable self-similar pulses and the result isplotted in FIG. 18 as a function of net cavity dispersion. In principle,250-nJ pulse energies are possible, if the second limitation permits it.Thus, a promising approach is to create new saturable absorbers where“over-driving” cannot occur. In essence, we need a saturable absorber ofwhich the transmittance is not a sinusoidal function of pulse energy.Surveying the landscape of saturable absorbers used in femtosecondlasers, the real saturable absorption in a semiconductor (for a recentreview sec [77]) is ideally suited for this purpose.

Semiconductor saturable absorbers (SSA's) are based on saturation of anoptical transition, and in contrast to NPE (which is based oninterference) they cannot be overdriven. Therefore, it should bepossible to obtain much higher pulse energies in fiber lasers if NPE isreplaced by a SSA. Historically, this was not feasible, becausesemiconductor structures capable of producing the large modulation depth(>10%) needed in a fiber laser did not exist. In addition, a practicalimpediment in the past was the lack of a commercial source of suchstructures—painstaking research was required to develop new ones.However, significant progress in the modulation depth has been made inthe last several years and there is now a commercial company that sellsSSA's. BATOP GmbH (Weimar, Germany) has emerged as a reliable source ofSSA's, with a variety of designs at reasonable prices (<$1 k/piece). Inparticular, structures with 80% modulation depth are available asstandard designs. It will be reasonably straightforward to incorporatethese structures in our lasers in place of NPE. The main work will beoptimizing the design of the structure for the target performancelevels.

A second major advantage of SSA's is that they are compatible withintegrated designs. The development of saturable absorbers that providefast and deep modulation will significantly facilitate the design ofall-fiber and environmentally-stable lasers. In principle, a femtosecondlaser could be constructed of segments of polarization-maintaining fiberthat provide gain and anomalous dispersion, and the saturable absorber.Fiber-pigtailed versions of SSA's are already commercially available.Such a laser would be as simple as possible, with no adjustments otherthan the pump power. We will design, construct and characterizehigh-power fiber lasers based on SSA's. Although the incorporation ofSSA with large modulation depth in a mode-locked fiber laser isrelatively new and there may be a number of practical issues to beaddressed in this work, the fundamental basis of the approach isestablished theoretically, and initial experiments in our lab withstructures from BATOP confirm that they perform as advertised. Thepromise of 25- to 50-nJ pulses directly from a robust and cost effectivefiber oscillator is highly significant. Thus, we will include thisdevelopment effort as a more exploratory component of this researchprogram, complementing our reliable (may even be commerciallyavailable), but inherently more expensive, approach of a fiber CPAsystem.

Aim 2: HOM Fiber Modules for SSFS.

We will design and develop novel HOM fiber modules for SSFS at inputwavelengths of 1030 nm and 775 nm. We will start by modifying theexisting HOM fiber design, and fabricate new fibers with the goal ofachieving 1- to 2-nJ output pulse energy. We will then extend the designspace to create new fibers that is capable of delivering 5- to 10-nJoutput pulses. OFS Laboratories has powerful, proprietary design toolsto design highly complex fibers—indeed, its market leadership indispersion compensating fibers was enabled by its ability to providerobust solutions for managing dispersion of the multitude oftransmission fibers used today. We realized that the design andfabrication of the HOM fiber module is the key enabling component forachieving our aims. We anticipate that several iterations will probablybe needed in the design and fabrication of the device before we canachieve the optimum performance. We have therefore set aside sufficientbudget to cover for the design and development cost for the HOM fibermodules. We note, however, the manufacturing process of the HOM fiber isentirely compatible with commercial silica fibers, making it anintrinsically low-cost approach. Thus, a low-cost device withtelecom-grade reliability is possible.

Tailoring HOM Fiber Dispersion for SSFS Applications

The physics of SSFS, as also seen from our preliminary results, dictatesthat the wavelength tuning range is limited by the dispersion-zerocrossings of the curves shown in FIGS. 8 and 14. Here we define Δλ_(zc)as the wavelength separation between the two dispersion zeros. Hence, toachieve the desired performance, the fibers would need Δλ_(zc) ˜300 nm,with maximum attainable value of D*A_(eff). Thus, the fiber designproblem reduces to one of realising a HOM fiber with the required valueof D*A_(eff) at the output wavelengths of the dispersion curve for eachof the two wavelength ranges and pulse-energy targets. The general fiberindex profile for achieving D_(w)>0 for the LP₀₂ mode is shown in FIG.19A. While FIG. 8 provided the physical intuition for D_(w)>0 in a HOMfiber, achieving target dispersion and A_(eff) values requires anumerical optimisation of the 6 parameters shown in FIG. 19A—namely, theindices of the 3 regions, and their dimensions. There are two ways toachieve a large dispersion (D) value—one is by increasing ΔN_(core) andΔN_(ring), but this may be at the expense of A_(eff): The secondapproach is by increasing r_(ring) as well as r_(trench). Increasingr_(ring) will enhance the mode size, while increasing r_(trench) willprovide for greater effective index changes as the mode transitions asdiscuss in section b, this will result in larger dispersion. We willperform extensive numerical optimisation to achieve the D*A_(eff)targets.

Dimensional scaling of the preform can also be used to shift thewaveguide dispersion D_(w). This is known for optical waveguides ascomplimentary scaling, which states that wavelength and dimension play acomplimentary role in the wave equation, and hence are interchangeable.However, note that this is true only for the waveguide component ofdispersion D_(w). Changes in material dispersion entail that the totalattained dispersion (D) is not wavelength scalable. In other words, tomove the dispersion curve that provides satisfactory operation in the1030-nm wavelength range to the ˜800-nm spectral range, we would needD_(w) high enough to counteract the strong negative trend for D_(m) aswavelength decreases. Hence, achieving similar properties at lowerwavelengths would need both the use of dimensional scaling and thedispersion-increasing recipes described above.

Our preliminary experimental results and numerical simulations showedthat HOM fiber modules for delivering 1- to 2-nJ output pulses cancertainly be made within the first 18 months of the grant period.Although these pulse energies are already sufficient for some biomedicalapplications, our ultimate aim is to produce fiber sources that arecapable of delivering 5- to 10-nJ pulse, making them crediblereplacements of the bulk solid state lasers.

To achieve 5- to 10-nJ output pulse energies, the fiber design will haveto be more aggressive than the existing design-class. Preliminarystudies of fiber design show that D*A_(eff) values of 5 to 10 times theexisting HOM module are achievable (FIG. 19B), therefore, increasing thesoliton pulse energy by 5 to 10 times (Eq. 1). The main difficulty is tosimultaneously achieve the large values of D*A_(eff) while maintainingΔλ_(zc)˜300 nm. We will overcome this difficulty by using one or more ofthe following three approaches:

1. Split the tuning range into two segments, and perform sequentialshifting with two different HOM fiber modules.

2. Increase ΔN_(core) and/or ΔN_(ring)—in general, increasing thesevalues will lead to larger tuning ranges.

3. Operate in even higher order modes—in general, D*A_(eff)monotonically increases with mode order. An even higher order mode leadsto a much higher D*A_(eff) value.

In approach 1, two different HOM fibers will be fabricated. The firstHOM fiber is optimized for the first half of the tuning range only. Thesecond HOM fiber module consists of the first HOM fiber fusion-splicedto another HOM fiber that is optimized for the second half of the tuningrange. Thus, the longest wavelength output from the first HOM fiber willbe used as the input to the second HOM fiber to achieve tuning in thesecond half of the wavelength range. To minimize perturbation to thesoliton, the D-values of the two HOM fibers at the transition wavelengthshould approximately be the same, i.e., the transition wavelength shouldbe located at the cross-over region of the two dispersion curves. FIG.19B (red and blue curves) shows one possible arrangement. By relaxingthe required wavelength range, each HOM fiber module can be optimizedfor maximum pulse energy. In fact, such sequential tuning scheme can beused repeatedly to further extend the tuning range and/or pulse energyif demanded by applications. Thus, with some added cost (two or more HOMfiber modules), this approach is certain to achieve our design goals.

Approaches 2 and 3 are both lower cost alternatives that can achieve therequired pulse energy in one HOM fiber module. The associated drawbackfor approaches 2 and 3 is that the HOM fiber would guide many higherorder modes, which may make it susceptible to mode coupling.Conventional wisdom states that fiber should be strictly single-moded toavoid modal interference problems. However, it had been demonstrated ina variety of applications, that specially designed HOM fibers areextremely robust to mode coupling, especially when the HOM is excitedwith the very high efficiencies that in-fiber gratings afford. As seenin our preliminary results with the existing HOM fiber, measuredconversion efficiencies of up to 99.9% are regularly achieved with thistechnology. Hence, the key to achieving operation with negligiblemodal-interference is (a) utilising the extreme efficiencies of LPGs toexcite only the desired HOM with purities exceeding 20 dB (99%), and (b)designing the fiber such that effective index spacing between thedesired mode and other parasitic/unwanted modes is large enough (theexact value depends on the application—km length propagation usuallyrequires modal index separations of ˜10⁻³, while an order-or-magnitudedecrease in this value can be tolerated when propagating over only 10 sto 100 s of meters). For example, we have achieved mode coupling levels˜0.1% in an LP₀₇ mode in a fiber that guided at least 49 other modes.This mode was found to be robust over lengths as long as 20 m [37],which is well beyond the length required (<10 m) for our applicationshere.

We further note that femtosecond pulses are generally quite tolerant tomode interferences due to the short coherence length. Modal dispersionwill generally separate the soliton pulse and the other modes in time sothat no interference can occur. Such a phenomenon has been observed infemtosecond pulse propagation in a large mode area fiber. We furthernote that a small amount of residue power in the other modes istypically not a concern for multiphoton excitation because of thequadratic (or even higher order) power dependence of the excitationprocess. Thus, it is entirely feasible to design a HOM fiber modulebased on even higher order modes such as the LP₀₇ mode that we havedemonstrated in the past. We believe that approaches 2 and 3 both have ahigh probability for success.

Our design process will also consider several practical issues, such asdeviations of fabricated profiles from the ideal design, sensitivity tovarious index and dimensional perturbations etc. This latter aspect isan important highlight of the design space we propose—since the HOMfiber is index guided, as opposed to band-gap guided, the dispersiveeffect is not strictly resonant in nature, and is much less sensitive toperturbations of the profile.

Fiber and Grating Fabrication

The key to achieving the desired properties is a mode that cantransition (as a function of wavelength) through well-defined, sharp,index steps in the profile. Therefore, the fabrication process must becapable of producing both large index steps as well as steep indexgradients (See FIG. 19A for the index profile). The ideal means toachieve this is the Modified Chemical Vapor Deposition (MCVD) process,which affords the best layer-by-layer control of refractive index of allestablished fabrication technologies for fibers. MCVD is the workhorsefabrication technique for fabricating transmission fibers throughout theworld today.

FIG. 20 shows an example of the designed and fabricated index profilesfor a HOM fiber that yields large positive dispersion in the 1060-nmwavelength range. The preform profiles closely match the design profilein both index values and the steep index gradients. Also shown in FIG.20 are index profiles from different sections of the preform—theexcellent uniformity of the MCVD process facilitates the realization ofHOM fibers whose properties are invariant as a function of fiber length.This robust fiber fabrication process is critical to provide a constantzero-dispersion wavelength in a HOM fiber for SSFS, and is a significantadvantage of this new design class in comparison to bandgap fibers.

Once a preform is fabricated, standard fiber-draw processes will be usedto obtain the fiber. The flexibility of the fiber draw process allowsfor drawing to a variety of non-standard fiber diameters—this afforddimensional scaling of the index profile, which in turn will allow forprecisely tuning the zero-dispersion wavelengths.

For device operation, a mode converter is needed, which will convert theincoming Gaussian-shaped, LP₀₁ mode into the desired LP₀₂ mode. Weachieve this with in-fiber LPGs. LPGs are permanently induced in fibersby lithographically transferring a grating pattern from an amplitudemask to the fiber using a UV laser [78]. For efficient gratingformation, the fiber is saturated with deuterium, which acts as acatalyst for the process which results in UV-induced index changes inGermanosilicate glasses. LPGs offer coupling between co-propagatingmodes of a fiber and have found a variety of applications as spectralshaping elements and mode-conversion devices. But LPGs are traditionallynarrow-band (as expected of any interferometric device), and while theyoffer strong (>99%) mode coupling, the spectral width of such couplingwas typically limited to a range of 0.5 to 2 nm, too narrow for afemtosecond pulse. To overcome the spectral limitation, reports haveshown that the LPG bandwidth can be extended to >60 nm [79] (˜500 nm, insome cases [80]) if the fiber waveguide were engineered to yield twomodes with identical group velocities. An example of a pair of broadbandmode-converter gratings employed with positive dispersion HOM fibers wasshown in FIG. 9—note that the large (51-nm) bandwidth was uniquelyenabled by the dispersive design of the fiber which enabled matching thegroup velocities of the two coupled modes.

Device Assembly

All the HOM fiber modules fabricated in this project will be similar ourexisting HOM fiber modules shown in FIG. 9C. At the input, the HOMfiber, with an LPG, is spliced to conventional SMF—this SMF can in factbe the output fiber of the source built in Aim 1. The SMF input ensuresthat only the LP₀₁ mode enters the HOM fiber, hence avoiding anyspurious mode coupling. Thereafter, the input grating provides strong(typically ranging from 99% to 99.99%-measured) mode conversion, henceobtaining the pure LP₀₂ mode.

At the output, a second LPG will be used to convert the beam back to aGaussian output. We will use the dispersion-matching designs that canyield ultra-large bandwidths. This will ensure the output pulse isalways converted back to a Gaussian profile, within the tuning range of˜250 nm. An important consideration for the output LPG is itslength—since the energetic output pulses are solitons for the specificcombination of dispersion and A_(eff) of the LP₀₂ mode, nonlineardistortions may occur when the signal goes to the (smaller A_(eff))fundamental LP₀₁ mode at the output. However, the length over which thesignal travels in the LP₀₁ mode, and hence the distortion itaccumulates, can be minimized—the high-index core of these HOM fibersenable LPG lengths of <5 mm, which implies that light resides in theLP₀₁ mode for <2.5 mm, hence largely avoiding nonlinear distortions.Note that the requirement for short LPGs actually complements the needfor broad bandwidth operation, since the conversion bandwidth istypically inversely proportional to the grating length.

Aim 3: System Demonstration.

We aim to demonstrate two all-fiber femtosecond sources with wavelengthtuning ranges of (1) 775 nm to 1000 nm and (2) 1030 nm to 1280 nm. Theoutput pulse energies will be first at 1 to 2 and then at 5 to 10 nJ. Wewill combine the femtosecond sources and the HOM fiber modules developedin Aims 1 and 2 into an all-fiber system. The fully integrated source isschematically shown in FIG. 21.

The intrinsic chirp from the fiber source (either a mode-locked fiberlasers or a CPA system), which was a major limitation in previous fibersystems, provides several key advantages for our system. First, itallows ˜10 m in the total length of the output fiber. Second, the highlychirped pulse makes the length of the single mode fiber pigtailinconsequential, eliminating the practical difficulties in cleaving andsplicing. Finally, the longer single mode fiber pigtail can alsoaccommodate additional fiber devices such as a variable fiber attenuatorand/or a fiber optic switch.

Second harmonic generation (SHG) will be employed to generatefemtosecond pulses at 775 nm. It was previously known that SHG with alinearly chirped fundamental pulse will result in a linearly chirped SHpulse [81], which can be subsequently compressed using lineardispersion. Interestingly, the final chirp-free SH pulse width isindependent of whether the compression is carried out before or afterthe SHG [81]. The conversion efficiency, however, is obviously higher ifthe chirped fundamental pulse is compressed before SHG. Because thedesigned pulse energy at the fundamental wavelength is high (at 10 to 50nJ/pulse), the conversion efficiency for SHG with the proposedexcitation source will be limited mostly by the depletion of thefundamental power, not by the available pulse peak intensity. Thus, SHGwill be highly efficient even with a chirped fundamental pulse withdurations of the order of several picoseconds if efficient doublingcrystals are employed [33, 82]. For example, with a periodically poledLiNbO₃ (PPLN), a conversion efficiency of 85%/nJ was demonstrated with230 fs pulses at 1550 nm [83]. Single-pass conversion efficiencies(energy efficiency) as much as 83% [84] and 99% [85] are demonstratedfor bulk and waveguide PPLN devices, respectively. Thus, SHG with achirped fundamental pulse can be used with the proposed femtosecondpulse source without the reduction in conversion efficiency, and, asdiscussed in the previous paragraph, has significant advantage in thesubsequent fiber optic delivery process. In addition, chirped SHG alsoeliminates the possibility of damaging to the doubling crystal due tothe high peak power of a femtosecond source. Photorefractive effects ofthe PPLN device is a concern at high average power (>500 mW), but sucheffects typically only occur at wavelength below 700 nm, and can bemitigated to a large extend by increasing the temperature of the crystaland/or by doping the crystal with Magnesium. To be conservative, we aretargeting a power conversion efficiency of ˜50% on a routine basis.

We will design systems using two different tuning mechanisms: 1. powertuning, and 2. length tuning. As shown in the preliminary results, bothtuning mechanisms offer similar tuning range (FIG. 15). The power tuningrequires only one HOM fiber module for the entire spectral range,however, the output power varies by approximately a factor of 3 (powerinput multiplied by the conversion efficiency). Although this powervariation across the tuning range is comparable to current femtosecondsystems like the Ti:S or Ti:S pumped OPO, it may nonetheless limit thepractical utility of the system, particularly at the smaller wavelengthshift where the output power is the lowest. Another approach is fiberlength tuning, which can essentially maintain the output power (FIG.15B, within +/−5%) across the entire spectral range. Fiber lengthtuning, however, requires multiple HOM fiber modules, increasing thesystem cost. An obvious compromise is to combine the two tuningmechanisms. As an alternative to the power tuning, we will design 2 to 3HOM fiber modules of different length, each optimized for power tuningover a ˜100-nm spectral range to maintain a reasonably constant output.Such a segmented tuning also simplifies the design of the output LPGssince a much narrower range of output wavelengths needs to be converted.It is interesting to note that such segmented tuning is similar to theearly generations of Ti:S lasers where multiple mirror sets wererequired to cover the entire tuning range. However, unlike a mirror-setexchange in a Ti:S laser, which would take an experienced operatorseveral hours to perform, the exchange of the HOM fiber modules wouldtake only a few seconds to connect the desired HOM fiber module to thesingle wavelength fiber source through a single mode fiber connector(see the connectorized output from a fiber source in FIG. 6), andrequire neither experience nor knowledge of the system. For a completelyelectronically controlled system, a simple fiber optic switch can beused to provide push-button HOM fiber module exchange. In fact, such atunable HOM fiber module has already been experimentally demonstratedseveral years ago for telecom applications [86]. We also note that, as asimple extension to the fiber length tuning, a HOM fiber module can alsobe designed to provide output at the input wavelength without SSFS. Insuch cases, the HOM fiber module simply serves as a delivery fiber forchirp compensation and pulse delivery.

The fiber-length tuning described above is obviously similar to thesequential tuning described in Aim 2 (approach 1) to achieve high pulseenergy. Both require multiple HOM fiber modules. In length tuning,however, the same HOM fiber of different lengths are used; while insequential tuning, two or more different HOM fibers are required.

Both power tuning and segmented length tuning require a mechanism tocontrol the incident power. SSFS is a nonlinear optical effect andeffectively happens instantaneously (<1 ps). Thus, the rate of thewavelength tuning of the proposed fiber source can be ultrafast, and iscompletely determined by the rate of power change. There are twoapproaches to adjust the power into the HOM fiber module. Mechanicalin-line fiber attenuators can achieve a tuning speed of ˜10 Hz, severalorders of magnitude faster than any existing laser systems. Because onlya small range of power adjustment is necessary for achieving the entirerange of wavelength tuning (less than a factor of 4 for power tuning),variable fiber attenuators that based on microbending can easily providethe speed and modulation depth required. Such a variable attenuator canbe calibrated so that rapid, electronically controlled wavelength tuningcan be achieved. We note that compact, electronically controlledvariable fiber attenuators are widely available commercially. Mostcommercial attenuators can provide modulation depth of ˜1000. Thus, wedo not anticipate any difficulty implementing the power controlmechanism. An alternative approach will be to use a fiber coupledelectro-optic modulator (EOM). Although such an approach will be moreexpensive (˜$2 k), it can easily provide nanosecond (i.e.,pulse-to-pulse) wavelength switching speed. In addition, such a devicealso provides the capability for fast (ns) laser intensity control. Toovercome the insertion loss of the electro-optic modulator, it can beplaced before the fiber amplifier in a CPA system. We also note thatthese EOMs are routinely used in telecommunications and are highlyrobust (telecom certified) and compact (the size of half a candy bar).Our proposed source can be readily configured to provide this high speedtuning capability.

We will perform detailed system testing and characterization, providingfeedbacks for iteration and optimization of our development efforts inAims 1 and 2. In particular, we will assess the wavelength and powerstability of the system. We are well aware the fact that SSFS is anonlinear optical effect; and nonlinear optical effects are generallysensitive to fluctuations in input power, pulse width, and pulsespectrum. We have taken this stability issue into our designconsiderations. First, we start with an all-fiber, single wavelengthfemtosecond source. One of the salient features of an all-fiber designis its stability. It is well known that a fiber laser is more stablethan a bulk solid state laser. Second, our fiber sources arespecifically designed for biomedical imaging applications. Because ofthe broad output pulse spectrum (10 to 20 nm) and the broad excitationpeaks of fluorescent molecules (tens of nm), a few nm of wavelengthshift is generally inconsequential. This is in sharp contrast toapplications such as precision frequency metrology, where even a smallfraction of an Angstrom spectral shift cannot be tolerated. Finally, thesoliton pulse shaping process is robust against fluctuations in theinput, which is one of the main reasons that solitons were used in longhaul communication systems. Our preliminary results in FIG. 13 alsoclearly demonstrate the robustness of SSFS. Even with a highly nonidcalinput pulse (FIG. 13 inset), a nearly perfect soliton pulse is obtainedat the output. In addition, simulations with a perfect Gaussian pulseinput showed good agreement with the experiments, particularly for theoutput at the soliton wavelength. Thus, we are confident about thestability of the proposed source. In the unlikely event thatunacceptably large power fluctuations are present, an alternativeapproach is to employ feedback stabilization. Because power adjustmentmechanisms are already needed for wavelength tuning, the only additioncomponent for feedback control is a photodiode for power monitoring (forexample, through a 1% fiber tap in the single mode pigtail before theLPG). Such a feedback control mechanism can largely eliminate powerdrifts on the slow time scale, ˜10 Hz for the mechanical variable fiberattenuator and MHz for the electro-optical intensity modulator. We notethat such a power stabilization scheme (“noise eater”) has already beencommercially implemented for a variety of laser systems. We do notanticipate any difficulty implementing the control mechanism ifnecessary.

Polarization control is another issue of practical concern. Forapplications that demand a linear input polarization, polarizationmaintaining (PM) fibers can be used throughout the system. Because theHOM fiber is fabricated within the conventional silica fiber platform,PM HOM fibers can be made using the same method designed forconventional PM fibers (such as adding stress rods to form a Pandafiber). For applications that demand adjustable input polarization,non-PM HOM fibers can be used and a simple in-line fiber polarizationcontroller can be used to adjust the output polarization state,eliminating the conventional free-space wave plate and/or polarizer.

There are several methods to remove the residue input light at theoutput of the HOM fiber module. Perhaps the simplest approach is todirectly deposit a dichroic coating (long wavelength pass) on the outputface of the fiber. Such coatings were often done for fiber lasers withlinear cavities and the deposition techniques were similar to that on aconventional glass substrate. After all, a silica fiber is a piece ofglass with a small diameter.

Aim 4: Biomedical Applications.

We will demonstrate the significance of our new femtosecond lasersources for biomedical applications of multiphoton microscopy,spectroscopy and endoscopy.

Our first stage demonstration involves “routine” multiphoton imaging andspectroscopy. We will compare the capability of the proposed tunablefiber source with our existing Ti:S lasers. We will verify the stabilityof the sources in imaging, especially since the two (and three)photon-dependence of excitation “amplifies” the effects of a fluctuatinglaser. In addition to multiphoton imaging, a potentially even moresensitive means to judge stability would be to test the laser as anexcitation source in fluorescence correlation spectroscopy (FCS)experiments, where laser noise (e.g. oscillations) would be very obvious(e.g. FCS measurements on the same sample made with our Ti:S compared toones carried out with our prototype laser). By installing our prototypelaser source on one or more multiphoton systems we will test the laserin the most practical way by using it in a routine day-to-day fashionfor a variety of imaging projects. Our main objective is to compare theimaging performance of MPM with the proposed sources and withconventional Ti:S lasers.

Our second stage demonstration experiments are designed to showcase theunique advantages of the proposed femtosecond sources, which haveseveral important functional attributes for multiphoton imaging notfound in the commonly used Ti:S laser. A review of the properties of thelasers being developed in Aims 1-3 and their importance to multiphotonimaging include: (1) all-fiber sources with integrated fiber delivery,(2) rapid, electronically controlled wavelength tuning, and (3)energetic pulses, particularly at the longer wavelength window of 1030to 1280 nm.

(1) All-Fiber Sources with Integrated Fiber Delivery.

The two femtosecond sources proposed are both all-fiber sources withintegrated single mode fiber-delivered (with >5 m of fiber length); thatis, the output of the sources could be directly fed into a microscopescanbox, an endoscope scanning system, or through a biopsy needle fortissue spectroscopy. For multiphoton microscopy this would greatlysimplify installation and maintenance of the system since alignmentwould be trivial; and for endoscopic imaging and spectroscopyapplications fiber-delivered illumination is clearly essential.

A stable fiber-delivered femtosecond source in the 780-850 nm range canbe directly incorporated in our current endoscope scanner design. Wealso note that the HOM fibers are highly resistant to bending loss, acharacteristic that is impossible to obtain in the large area mode fiberpreviously demonstrated for pulse delivery [24]. Thus, it isparticularly suited for small diameter, flexible endoscopes where bendradius as small as ˜1 cm is necessary. Although no clinical experimentis planned within the scope of this program, the long fiber deliverylength (˜6 m) allows the source to be at a remote location away from theoperating room. In a clinical environment, such a physical separationoffers major practical advantages, such as eliminating the complicationsof sterilization, ultimately leading to a much reduced cost.

The HOM fiber that provides the dispersion compensation and wavelengthtuning through SSFS can also be simultaneously used as the delivery andcollection fiber for tissue spectroscopy. The diameter of the opticalfiber is ˜0.125 mm (standard size for a single mode fiber), which ismuch smaller than the inside diameter of an 18 or 20 gauge needle thatis routinely used for core biopsy. The excited signal will be collectedby the same fiber. A fiber wavelength division multiplexer (WDM) can beplaced between the fixed wavelength femtosecond source and the HOM fibermodule to direct the collected signal to the detecting unit, whichconsists a grating and a CCD. In addition, the rapid wavelength tuningcapability allows the emission spectrum of the tissue to be recorded asa function of the excitation wavelength. These multiphoton excitedfluorescence excitation-emission matrix (EEM) can potentially provideunique diagnostic signatures for cancer detection just as one-photon EEMdoes [87, 88]. FIG. 22 shows schematically such an all-fiber,multiphoton excited needle biopsy [89] setup. The long delivery fiber(HOM fiber) once again allows the excitation and detection apparatus tobe at locations away from the operating room. We further note that adouble-clad fiber structure with the HOM fiber as the guiding core canbe easily fabricated to improve signal collection efficiency [26]because of the all-silica fiber design.

One potential complication of the proposed tunable source formultiphoton EEM is the power and pulse width variation across the entiretuning range. Calibration using a known multiphoton excitation standard,such as fluorescein dye, will be carried out before experimentation onbiological samples. Such a calibration procedure is routinely used inprevious multiphoton spectroscopy work. Multiphoton excitation standardshave been established in the past and has extensive experience inmultiphoton spectroscopy [71]. We don't expect significant problems inthe calibration of the instrument.

Application of MPM in early cancer detection using a transgenic mouseline in which tumor formation is initiated by the conditionalinactivation of the p53 and Rb1 genes by Adenovinis-Cre-mediatedrecombination has been reported [90]. The experiment on endoscopes andtissue spectroscopy through needle biopsies is highly synergistic withthe on-going cancer research and provides an ideal platform forshowcasing the “all-fiber” characteristics of the proposed femtosecondsource.

(2) Rapid, Electronically Controlled Wavelength Tuning.

A unique capability of the proposed sources is the ability to rapidlytune the wavelength much faster than currently possible with single boxTi:S systems. Rapid wavelength tuning would allow for line by lineswitching between excitation wavelengths during scanning, or forcollecting excitation spectra, a potentially important parameter forbiomedical applications that may utilize intrinsic fluorophores withoverlapping emissions, but differing excitation spectra.

By synchronizing the wavelength control with the scanning andacquisition, we will modify one of our imaging systems to enable onewavelength during the “forward” line and a second during the return(without changing the Y position). This is analogous to what is nowstandard on modern AOM-equipped confocal microscopes, where, forexample, a green dye is excited with 488 nm excitation in one directionand 547 nm excitation to excite a different dye during the return. Inthis way a two-color image can be collected using dyes with differentexcitation maximums and separable emissions. The temporal aspecteliminates problems with spectral cross-talk in many cases. Althoughmultiphoton cross-sections for many dyes are broad often allowing forexcitation of different dyes at the same wavelength (usually due tooverlapping UV bands, so this normally only works at 800 nm or shorter),the ability to rapidly switch between wavelengths anywhere between 780and 1000 nm would be an important enhancement for many dyes pairs. Afterinterfacing the wavelength control with our scanning systems we willapply this capability in pilot experiments with fluorophores such as CFPand GFP which have different two photon excitation maxima, but partiallyoverlapping emission spectra (FIG. 23).

As an added benefit, the EOM device that enables rapid wavelength tuningcan also be used to provide fast switching and modulation of theexcitation beam. At a minimum this functionality should be comparable towhat we currently achieve using our 80-mm resonance-dampened KTP* Pockelcells for routine beam blanking and intensity control (microsecondswitching). Available fiber-coupled EOMs can switch in thesub-nanosecond range and should allow for a laser with a built-inmodulator that would enable the user to reduce the effective laserrepetition rate for measurements of fluorescent decays times andfluorescent lifetime imaging (FLIM), as well as for the more standardmodulation needs. After implementing the required control electronics,we will use this functionality for routine beam blanking and control,photobleaching recovery measurements, and FLIM.

Another intriguing possibility provided by SSFS is that multiplewavelength tunable pulses can be obtained from the same fixed wavelengthfiber source. For example, the output of the fixed wavelengthfemtosecond fiber source can be split into two halves and each halfpropagates through a HOM fiber module. The two HOM fiber modules can bethe same (use power tuning) or of different lengths (length tuning).Such a multi-color femtosecond source opens a range of newopportunities, such as two-color two-photon excitation [9-94] andcoherent anti-Stokes Raman scattering (CARS) imaging [95], where twosynchronized ultrafast sources are needed previously. The spectralbandwidths directly from the proposed sources will likely be too largefor CARS, possibly requiring spectral filtering or shaping.

(3) Energetic Pulses at the Longer Wavelength Window of 1030 to 1280 nm.

The proposed longer wavelength femtosecond source offers unprecedentedcapability at the wavelength window of 1030 to 1280 nm. Although thereare only a few experimental works for multiphoton imaging beyond 1100nm, longer wavelength multiphoton imaging is feasible and canpotentially offer significant advantage in deep tissue imaging,particularly with the high pulse energy we will be able to obtain.Efforts are underway on exploring this new spectral window for MPM,using the existing Ti:S pumped OPO. We will demonstrate the capabilityof the proposed femtosecond source for imaging in the 1.27 μm regionusing indicators such as shown in FIG. 16 and IR quantum dots. We willcompare these results with what we currently achieve using the OPOsystem. We aim to achieve unprecedented imaging depth using theenergetic pulses from our source. There is no doubt that the creation ofan all-fiber, wavelength tunable, energetic femtosecond source at thelonger wavelength window of 1030 to 1280 nm will open significant newopportunities for biomedical imaging.

LITERATURE

All of the references listed below are hereby incorporated by referencein their entirety. These references are indicated herein above as beingenclosed by brackets.

-   1. Göppert-Mayer, M., Über Elementarakte mit zwei Quantensprüngen.    Ann. Physik., 1931. 9: p. 273-295.-   2. Kaiser, W. and C. G. B. Garrett, Two-photon excitation in CaF    ₂:Eu²⁺. Phys. Rev. Lett., 1961. 7: p. 229.-   3. Denk, W., J. H. Strickler, and W. W. Webb, Two-photon laser    scanning fluorescence microscopy. Science, 1990. 248: p. 73-76.-   4. Valdmanis, J. A. and R. L. Fork, Design considerations for a    femtosecond pulse laser balancing self phase modulation, group    velocity dispersion, saturable absorption, and saturable gain.    IEEE. J. Quantum Electron, 1986. QE-22: p. 112-118.-   5. Spence, D. E., P. N. Kean, and W. Sibbett, 60-fsec pulse    generation from a self-mode-locked Ti:sapphire laser. Opt.    Lett., 1991. 16: p. 42.-   6. Yuste, R. and W. Denk, Dendritic spines as basic function units    of neuronal integration. Nature, 1995. 375: p. 682-684.-   7. Williams, R. M., D. W. Piston, and W. W. Webb, Two-photon    molecular excitation provides intrinsic 3-dimensional resolution for    laser-based microscopy and microphotochemistry. FASEB J., 1994.    8(11): p. 804-813.-   8. Denk, W., D. W. Piston, and W. W. Webb, Two-photon molecular    excitation in laser scanning microscopy, in The handbook of Confocal    Microscopy, J. Pawley, Editor. 1995, Plenum: New York. p. 445-458.-   9. Masters, B. R., Selected papers on multiphoton excitation    microscopy. 2003, Bellingham: SPIE press.-   10. Helmchen, F. and W. Denk, Deep tissue two-photon microscopy.    Nat. Methods, 2005. 2: p. 932-940.-   11. Xu, C., W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb,    Multiphoton fluorescence excitation: new spectral windows for    biological nonlinear microscopy. Proc. Nat. Acad. Sci. USA, 1996.    93: p. 10763-10768.-   12. Wokosin, D. L., V. E. Centonze, S. Crittenden, and J. G. White,    Three-photon excitation of blue-emitting fluorophores by laser    scanning microscopy. Mol. Biol. Cell, 1995. 6: p. 113a.-   13. Hell, S. W., K. Bahlmann, M. Schrader, A. Soini, H. Malak, I.    Gryczynski, and J. R. Lakowicz, Three-photon excitation in    fluorescence microscopy. J. Biomed. Opt., 1996. 1: p. 71-74.-   14. Maiti, S., J. B. Shear, and W. W. Webb, Multiphoton excitation    of amino acids and neurotransmitters: a prognosis for in situ    detection. Biophys. J., 1996. 70: p. A210.-   15. Campagnola, P. J., M. D. Wei, A. Lewis, and L. M. Loew,    High-resolution nonlinear optical imaging of live cells by second    harmonic generation. Biophys J., 1999. 77: p. 3341-3349.-   16. Moreaux, L., O. Sandra, and J. Mertz, Membrane imaging by second    harmonic generation microscopy. J. Opt. Soc. Am. B, 2000. 17: p.    1685-1694.-   17. Muller, M., J. Squier, K. R. Wilson, and G. J. Brakenoff, 3D    microscopy of transparent objects using third-harmonic    generation. J. Microsc., 1998. 191: p. 266-274.-   18. Erik J. Sánchez, L. N., and X. Sunney Xie, Near-field    fluorescence microscopy based on two-photon excitation with metal    tips. Phys. Rev. Lett., 1999. 82: p. 4014.-   19. Jung, J. C. and M. J. Schnitzer, Multiphoton endoscopy. Opt.    Lett., 2003. 28(11): p. 902.-   20. Boppart, S. A., T. F. Deutsch, and D. W. Rattner, Optical    imaging technologies in minimally invasive surgery. Surg    Endosc, 1999. 13: p. 718-722.-   21. Liang, C., M. Descour, K. Sung, and R. Richards-Kortum, Fiber    confocal reflectance microscopy (FCRM) for in vivo imaging. Opt.    Exp., 2001. 9(13): p. 821-830.-   22. Sung, K., C. Liang, M. Descour, T. Collier, M. Follen, and R.    Richards-Kortum, Fiber-optic confocal reflectance microscopy with    miniature objective for in vivo imaging of human tissues. IEEE    Trans. Biomed. Eng., 2002. 49(10): p. 1168-1172.-   23. Flusberg, B. A., E. D. Cocker, W. Piyawattanametha, J. C.    Jung, E. L. M. Cheung, and M. J. Schnitzer, Fiberoptic fluorescence    imaging. Nature Methods, 2005. 2(12): p. 941-950.-   24. Ouzounov, D. G., K. D. Moll, M. A. Foster, W. R. Zipfel, W. W.    Webb, and A. L. Gaeta, Delivery of nanojoule femtosecond pulses    through large-core microstructure fiber. Opt. Lett., 2002.    27(17): p. 1513-1515.-   25. Helmehen, F., M. S. Fcc, D. W. Tank, and W. Denk, A miniature    head-mounted two-photon microscope: high resolution brain imaging in    freely moving animals. Neuron, 2001. 31: p. 903-912.-   26. Fu, L., X. Gan, and M. Gu, Nonlinear optical microscopy based on    double-clad photonic crystal fibers. Opt. Express, 2005. 13: p.    5528-5534.-   27. Denk, W., K. R. Delaney, A. Gelperin, D. Kleinfeld, B. W.    Strowbridge, D. W. Tank, and R. Yuste, Anatomical and functional    imaging of neurons using 2-photon laser scanning microscopy. Journal    of Neuroscience Methods, 1994. 54(2): p. 151-162.-   28. Squirrell, J. M., D. L. Wokosin, J. G. White, and B. D.    Bavister, Long-term two-photon fluorescence imaging of mammalian    embryo without compromising viability. Nature Biotechnol., 1999.    17(8): p. 763-767.-   29. Zipfel, W. R., R. M. Williams, R. Christie, A. Y. Nikitin, B. T.    Hyman, and W. W. Webb, Live tissue intrinsic emission microscopy    using multiphoton-excited native fluorescence and second harmonic    generation. Proc Natl Acad Sci USA, 2003. 100(12): p. 7075-80.-   30. Theer, P., M. T. Hasan, and W. Denk, Two-photon imaging to u    depth of 1000 μm in living brains by use of a Ti:Al₂O³ regenerative    amplifier. Opt. Lett., 2003. 28: p. 1022-1024.-   31. Curley, P. F., A. I. Ferguson, J. G. White, and W. B. Amos,    Application of a femtosecond self-sustaining mode-locked Ti:sapphire    laser to the field of laser scanning confocal microscopy. Optical    and quantum electronics, 1992. 24: p. 851-859.-   32. Zipfel, W. R., R. M. Williams, and W. W. Webb, Nonlinear magic:    multiphoton microscopy in the biosciences. Nat Biotechnol, 2003.    21(11): p. 1369-77.-   33. Fermann, M. E., A. Galvanauskas, U. Sucha, and D. Harter,    Fiber-lasers for ultrafast optics. Appl. Phys. B, 1997. 65: p.    259-275.-   34. Nelson, L. E., D. J. Jones, K. Tamura, H. A. Haus, and E. P.    Ippen, Ultrashort-pulse fiber ring lasers. App. Phys. B, 1997.    65: p. 277-294.-   35. Lim, H., F. O. Ilday, and F. Wise, Generation of 2-nJ pulses    from a femtosecond ytterbium fiber laser. Opt. Lett., 2003. 28: p.    660-662.-   36. Strickland, D. and G. Mourou, Compression of amplified chirped    optical pulses. Opt. Commun., 1985. 56: p. 219.-   37. Ramachandran, S., J. W. Nicholson, S. Ghalmi, M. F. Yan, P.    Wisk, E. Monberg, and F. V. Dimarcello, Light propagation with    ultra-large modal areas in optical fibers. Opt, Lett., 2006. 31.-   38. Gordon, J., Theory of the soliton self-frequency shift. Opt.    Lett., 1986. 11: p. 662-664.-   39. Knight, J. C., T. A. Birks, P. S. J. Russell, and D. M. Atkin,    All-silica single-mode optical fiber with photonic crystal cladding.    Opt. Left., 1996. 21: p. 1547-1549.-   40. Knight, J. C., J. Broeng, T. A. Birks, and P. S. J. Russell,    Photonic band gap guidance in optical fibers. Science, 1998. 282: p.    1476-1478.-   41. Liu, X., C. Xu, W. H. Knox, J. K. Chandalia, R. J.    Eggleton, R. S. Windier, and S. G. Kosinski, Soliton self-frequency    shift in a short tapered air-silica microstructure fiber. Opt.    Lett., 2001. 26(6): p. 358-360.-   42. Lim, H., J. Buckley, A. Chong, and F. W. Wise, Fiber-based    source of femtosecond pulses tunable from 1.0 to 1.3 microns.    Electron. Lett., 2004. 40: p. 1523.-   43. Ouzounov, D. G., F. R. Ahmad, D. Muller, N. Venkataraman, M. T.    Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, and A. L. Gaeta,    Generation of megawatt optical solitons in hollow-core photonic    band-Gap fibers. Science, 2003. 301: p. 1702-1704.-   44. Agrawal, G. P., Nonlinear fiber optics. 2nd ed. Optics and    Photonics, ed. P. F. Liao, P. L. Kelly, and I. Kaminow. 1995, New    York: Academic Press.-   45. Knight, J. C., J. Arriaga, T. A. Birk, A. Ortigosa-Blanch, W. J.    Wadsworth, and P. S. J. Russel, Anomalous dispersion in photonic    crystal fiber. IEEE Photon. Technol. Lett., 2000. 12: p. 807.-   46. Foster, M. A., A. L. Gaeta, Q. Cao, and R. Trebino,    Soliton-effect compression of supercontinuum to few-cycle durations    in photonic nanowires. Opt. Exp., 2005. 13: p. 6848-6855.-   47. Lim, H., F. O. Ilday, and F. W. Wise, Control of dispersion in a    femtosecond ytterbium laser by use of photonic bandgap fiber. Opt.    Express, 2004. 12: p. 2231.-   48. Ramachandran, S., Dispersion-tailored few-mode fibers: a    versatile platform for in-fiber photonic devices. J. Lightwave.    Technol., 2005. 23: p. 3426.-   49. Ramachandran, S., B. Mikkelsen, L. C. Cowsar, M. F. Yan, G.    Raybon, L. Boivin, M. Fishteyn, W. A. Reed, P. Wisk, D.    Brownlow, R. G. Huff, and L. Gruner-Nielsen, All-fiber,    grating-based, higher-order-mode dispersion compensator for    broadband compensation and 1000-km transmission at 40 Gb/s. IEEE    Photoic. Technol. Lett., 2001. 13: p. 632.-   50. Xu, C. and W. W. Webb, Multiphoton excitation of molecular    fluorophores and nonlinear laser microscopy, in Topics in    fluorescence spectroscopy, J. Lakowicz, Editor. 1997, Plenum Press:    New York. p. 471-540.-   51. Ilday, F. O., J. Buckley, H. Lim, and F. W. Wise, Generation of    50-fs, 5-nJ pulses at 1.03 m from a wave-breaking-free fiber laser.    Opt, Lett., 2003. 28: p. 1365-1367.-   52. Buckley, J., F. W. Wise, F. O. Ilday, and T. Sosnowski,    Femtosecond fiber lasers with pulse energies above 10 nJ. Opt,    Lett., 2005. 30: p. 1888.-   53. Ilday, F. O., J. Buckley, F. W. Wise, and W. G. Clark,    Self-similar evolution of parabolic pulses in a laser. Phys. Rev.    Lett., 2004. 92: p. 213902.-   54. Jones, D. J., H. A. Haus, L. E. Nelson, and E. P. Ippen,    Stretched-pulse generation and propagation. IEICE Trans.    Electron, 1998. E81-C: p. 180.-   55. Lim, H., F. O. Ilday, and F. W. Wise, Femtosecond ytterbium    fiber laser with photonic crystal fiber for dispersion control. Opt.    Express, 2002. 10: p. 1497.-   56. Lim, H., A. Chong, and F. W. Wise, Environmentally-stable    femtosecond fiber laser with birefringent photonic bandgap fiber.    Opt. Express, 2005. 13: p. 3460.-   57. Ramachandran, S., S. Ghalmi, J. W. Nicholson, M. F. Yan, P.    Wisk, E. Monberg, and F. V. Dimarcello. Demonstration of Anomalous    Dispersion in a Solid, Silica-based Fiber at λ<1300 nm. in Proc.    Optical Fibers Comm. 2006. Annaheim, Calif.-   58. Gruner-Nielsen, L., M. Wandel, P. Kristensen, C.    Jφrgensen, L. V. Jφrgensen, B. Edvold, B. Pálsdóttir, and D.    Jakobsen, Dispersion-compensating fibers. J. Lightwave.    Technol., 2005. 23: p. 3566.-   59. Menashe, D., M. Tur, and Y. Danziger, Interferometric technique    for measuring dispersion of higher order modes in optical fibres.    Electron. Lett., 2001. 37(1439).-   60. Hatami-Hanza, H., J. Hong, A. Atieh, P. Myslinski, and J.    Chrostowski, Demonstration of all-optical demultiplexing of a    multilevel soliton signal employing soliton decomposition and self    frequency shift. IEEE Photon. Technol. Lett., 1997. 9(6): p.    833-835.-   61. Goto, T. and N. Nishizawa, Compact system of wavelength-tunable    femtosecond soliton pulse generation using optical fibers. IEEE    Photon. Technol. Lett., 1999. 11: p. 325-328.-   62. Price, J. H., K. Furasawa, T. M. Monro, L. Lefort, and D. J.    Richardson, Tunable, femtosecond pulse source operating in the tange    of 1.06-1.33 μm based on an Yb-doped holey amplifier. J. Opt. Soc.    Am. B, 2002. 19(6): p. 1286-1294.-   63. Nishizawa, N., Y. Ito, and T. Goto, 0.78-0.90-μm    wavelength-tunable femtosecond soliton pulse generation using    photonic crystal fiber. IEEE Photoic. Technol. Lett., 2002.    14(7): p. 986-988.-   64. Xu, C. and X. Liu, Photonic analog-to-digital converter using    soliton self-frequency shift and interleaving spectral filters. Opt.    Lett., 2003. 28: p. 986-988.-   65. Andersen, E. R., V. Birkedal, J. Thogersen, and S. R. Keiding,    Tunable light source for coherent anti-stokes Raman scattering    microspectroscopy based on soliton self-frequency shift. Opt,    Lett., 2006. 31(9): p. 1328-1330.-   66. McConnel, G. and E. Riis, Photonic crystal fiber enables    short-wavelength two-photon laser scanning microscopy with fura-2.    Phys. Med. Biol., 2004. 49: p. 4757-4763.-   67. Chandalia, J. K., B. J. Eggleton, R. S. Windier, S. G.    Kosinski, X. Liu, and C. Xu, Adiabatic coupling in tapered    air-silica microstructured optical fiber. IEEE Photon. Technol.    Lett., 2001. 13: p. 52-54.-   68. Skryabin, D. V., F. Luan, J. C. Knight, and P. S. J. Russel,    Soliton self-frequency shift cancellation in photonic crystal    fibers. Science, 2003. 301: p. 1705-1708.-   69. Cheong, W. F., S. A. Prahl, and A. J. Welch, A review of the    optical properties of biological tissues. IEEE J. Quantum    Electron., 1990. 26(12): p. 2166-2185.-   70. Sun, C., C. C., S. Chu, T. Tsai, Y. Chen, and B. Lin,    Multiharmonic-generation biopsy of skin. Opt. Lett., 2003. 28: p.    2488-2490.-   71. Xu, C. and W. W. Webb, Measurement of two-photon excitation    cross-sections of molecular fluorophores with data from 690 nm to    1050 nm. J. Opt. Soc. Am. B, 1996. 13: p. 481-491.-   72. Chu, S., 1. Chen, T. Liu, P. Chen, and C. Sun, Multimodal    nonlinear spectral microscopy based on a femtosecond Cr:forsterite    laser. Opt. Lett., 2001. 26: p. 1909-1911.-   73. Dunn, A. K., V. P. Wallace, M. Coleno, M. W. Berns, and B. J.    Tromberg, Influence of optical properties on two-photon fluorescence    imaging in turbid sample. Appl. Opt., 2000. 39(7): p. 1194-1201.-   74. Beaurepaire, E. and J. Mertz, Epifluorescence collection in    two-photon microscopy. Appl. Opt., 2002. 41(25): p. 5376-5382.-   75. van Howe, J., G. Zhu, and C. Xu, Compensation of self-phase    modulation in fiber-based chirped-pulse amplification systems. Opt,    Lett., 2006. 31: p. 1756-1758.-   76. Zhou, S., L. Kuznctsova, A. Chong, and F. Wise, Opt. Exp., 2005.    13: p. 4869.-   77. Keller, U., Recent developments in compact ultrafast lasers.    Nature, 2003. 424: p. 831.-   78. Vengsarkar, A. M., P. L. Lemaire, J. B. Judkins, V. Bhatia, T.    Erdogan, and J. E. Sipe, J. Lightwave. Technol., 1996. 14: p. 58.-   79. Ramachandran, S., Z. Wang, and M. F. Yan, Bandwidth control of    long-period grating-based mode-converters in few-mode fibers. Opt,    Lett., 2002. 27: p. 698.-   80. Ramachandran, S., M. F. Yan, E. Monberg, F. V. Dimarcello, P.    Wisk, and S. Ghalmi, Record bandwidth microbend gratings for    spectrally flat variable optical attenuators. IEEE Photoic. Technol.    Lett., 2003. 15: p. 1561.-   81. Sidick, E., A. Dienes, and A. Knoesen, Ultrashort-pulse second    harmonic generation. II. Nontransform-limited fundamental pulses. J.    Opt. Soc. Am. B, 1995. 12(9): p. 1713-1722.-   82. Imeshev, G., M. A. Arbore, M. M. Fejer, A. Galvanauskas, M. E.    Fermann, and D. Harter, Ultrashort-pulse second-harmonic generation    with longitudinally nonuniform quaso-phase matching grating: pulse    compression and shaping. J. Opt. Soc. Am. B, 2000. 17(2): p.    304-318.-   83. Arbore, M. A., M. M. Fejer, M. E. Fermann, A. Hariharan, A.    Galvanauskas, and D. Hader, Frequency doubling of femtosecond    erbium-fiber lasers in periodically poled lithium niobate. Opt.    Lett., 1997. 22(1): p. 12-15.-   84. Taverner, D., P. Britton, P. G. R. Smith, D. J.    Richardson, G. W. Ross, and D. C. Hana, Highly efficient    second-harmonic and sum-frequency generation of nanosecond pulses in    a cascaded erbium-doped fiber:periodically poled lithium niobate    source. Opt. Lett., 1998. 23(3): p. 162-164.-   85. Parameswaran, K. R., J. R. Kurz, R. V. Roussev, and M. M. Fejer,    Observation of 99% oump depletion in single-pass second-harmonic    generation in a periodically poled lithium niobate waveguide. Opt.    Left., 2002. 27(1): p. 43-45.-   86. Ramachandran, S., S. Ghalmi, S. CHandrasekhar, I.    Ryazansky, M. F. Yan, F. V. Dimarcello, W. A. Reed, and P. Wisk,    Tunable dispersion compensators utilizing higher order mode fibers.    IEEE Photoic. Technol. Lett., 2003. 15; p. 727-729.-   87. Ramanujam, N., Fluorescence spectroscopy of neoplastic and    non-neoplastic Tissues. Neoplasia, 2000. 2: p. 89-117.-   88. Chang, S. K., M. Follen, A. Malpica, U. Utzinger, G.    Staerkel, D. Cox, E. N. Atkinson, C. MacAulay, and R.    Richards-Kortum, Optimal excitation wavelengths for discrimination    of cervical neoplasia. IEEE Trans. Biomed Eng., 2002. 49: p.    1102-1111.-   89. Li, X., C. Chudoba, T. Ko, C. Pitris, and J. G. Fujimoto,    Imaging needle for optical coherence tomography. Opt, Lett., 2000.    25: p. 1520-1522.-   90. Flesken-Nikitin, A., K. C. Choi, J. P. Eng, E. N. Shmidt,    and A. Y. Nikitin, Induction of carcinogenesis by concurrent    inactivation of p53 and Rb1 in the mouse ovarian surface epithelium.    Cancer Res, 2003. 63(13): p. 3459-63.-   91. Lakowicz, J. R., 1. Gryczynski, H. Malak, and Z. Gryczynski,    Two-color two-photon excitation of fluorescence. Proc. SPIE, 1997.    2980: p. 368-380.-   92. Chen, J. and K. Midorikawa, Two-color two-photon 4Pi    fluorescence microscopy. Opt. Lett., 2004. 29(12): p. 1354-1356.-   93. Caballero, M. T., P. Andrés, A. Pons, J. Lancis, and M.    Martinez-Corral, Axial resolution in two-color excitation    fluorescence microscopy by phase-only binary apodization. Opt.    Commun., 2005. 246: p. 313-321.-   94. Mar Blanca, C. and C. Saloma, Two-color excitation fluorescence    microscopy through highly scattering media. Appl. Opt., 2001. 40: p.    2722-2729.-   95. Potma, E. O., D. J. Jones, J. Cheng, X. S. Xic, and J. Ye, High    sensitivity coherent anti-stokes Raman scattering microscopy with    two tightly sychronized picosecond lasers. Opt. Lett., 2002. 25: p.    1168-1170.

Although preferred embodiments have been depicted and described indetail herein, it will be apparent to those skilled in the relevant artthat various modifications, additions, substitutions, and the like canbe made without departing from the spirit of the invention and these aretherefore considered to be within the scope of the invention as definedin the claims which follow.

1. An apparatus for producing optical pulses of a desired wavelength,said apparatus comprising: an optical pulse source operable to generateinput optical pulses at a first wavelength; and a higher-order-mode(HOM) fiber module operable to receive the input optical pulses at thefirst wavelength and thereafter to produce output optical pulses at thedesired wavelength by soliton self-frequency shift (SSFS).
 2. Theapparatus according to claim 1, wherein the HOM fiber module comprisesan HOM fiber.
 3. The apparatus according to claim 2, wherein the HOMfiber is a solid silica-based fiber.
 4. The apparatus according to claim1, wherein the HOM fiber module comprises an HOM fiber and at least onemode converter.
 5. The apparatus according to claim 4, wherein the atleast one mode converter is connectedly disposed between the opticalpulse source and the HOM fiber.
 6. The apparatus according to claim 5further comprising: a second mode converter terminally connected to theHOM fiber.
 7. The apparatus according to claim 4, wherein the at leastone mode converter is a long period grating (LPG).
 8. The apparatusaccording to claim 1, wherein the optical pulse source generates inputoptical pulses having a pulse energy of at least 1.0 nanojoules (nJ). 9.The apparatus according to claim 1, wherein the optical pulse sourcegenerates input optical pulses having a pulse energy of between about1.0 nJ and about 100 nJ.
 10. The apparatus according to claim 1, whereinthe optical pulse source comprises either a mode-locked laser or achirped pulse amplification (CPA) system.
 11. The apparatus according toclaim 10, wherein the mode-locked laser is a mode-locked fiber laser.12. The apparatus according to claim 10, wherein the CPA system is afiber CPA system.
 13. The apparatus according to claim 1, wherein theoptical pulse source generates input optical pulses such that the firstwavelength is a wavelength within the transparent region of asilica-based fiber.
 14. The apparatus according to claim 13, wherein thefirst wavelength is below 1300 nanometers (nm).
 15. The apparatusaccording to claim 13, wherein the first wavelength is a wavelengthbetween the range of about 300 nm and about 1300 nm.
 16. The apparatusaccording to claim 1, wherein the optical pulse source generates inputoptical pulses having a subpicosecond pulse width.
 17. The apparatusaccording to claim 1, wherein the HOM fiber module produces outputoptical pulses having a pulse energy of at least 1.0 nJ.
 18. Theapparatus according to claim 1, wherein the HOM fiber module producesoutput optical pulses such that the desired wavelength is a wavelengthwithin the transparent region of a silica-based fiber.
 19. The apparatusaccording to claim 18, wherein the desired wavelength is below 1300 nm.20. The apparatus according to claim 18, wherein the desired wavelengthis a wavelength between the range of about 300 nm and about 1300 nm. 21.The apparatus according to claim 1, wherein the HOM fiber moduleproduces output optical pulses having a subpicosecond pulse width. 22.The apparatus according to claim 1 further comprising: a power controlsystem connectedly disposed between the optical pulse source and the HOMfiber module.
 23. The apparatus according to claim 22, wherein the powercontrol system achieves subnanosecond power tuning of the firstwavelength.
 24. The apparatus according to claim 23, wherein the powercontrol system comprises a lithium niobate intensity modulator device.25. The apparatus according to claim 1 further comprising: a single-modefiber (SMF) connectedly disposed between the optical pulse source andthe HOM fiber module.
 26. The apparatus according to claim 1, whereinthe HOM fiber module produces output optical pulses that can penetrateanimal or plant tissue at a penetration depth of at least 0.1millimeters (mm).
 27. The apparatus according to claim 1 furthercomprising: an endoscope terminally associated with the HOM fibermodule.
 28. The apparatus according to claim 1 further comprising: anoptical biopsy needle terminally associated with the HOM fiber module.29. The apparatus according to claim 1 further comprising: a multiphotonmicroscope system functionally associated with the apparatus.
 30. Theapparatus according to claim 1 further comprising: a multiphoton imagingsystem functionally associated with the apparatus.
 31. A method ofproducing optical pulses having a desired wavelength, said methodcomprising: generating input optical pulses using an optical pulsesource, wherein the input optical pulses have a first wavelength and afirst spatial mode; and delivering the input optical pulses into ahigher-order-mode (HOM) fiber module to alter the wavelength of theinput optical pulses from the first wavelength to a desired wavelengthby soliton self-frequency shift (SSFS) within the HOM fiber module,thereby producing output optical pulses having the desired wavelength.32. The method according to claim 31, wherein the HOM fiber modulecomprises an HOM fiber.
 33. The method according to claim 32, whereinthe HOM fiber is a solid silica-based fiber.
 34. The method according toclaim 32 further comprising: converting the first spatial mode of theinput optical pulses into a second spatial mode prior delivering theinput optical pulses into the HOM fiber so that the output opticalpulses have the second spatial mode, wherein the first spatial mode andthe second spatial mode are different modes.
 35. The method according toclaim 34 further comprising: reconverting the second spatial mode of theoutput optical pulses back to the first spatial mode.
 36. The methodaccording to claim 31, wherein the optical pulse source generates inputoptical pulses having a pulse energy of at least 1.0 nanojoules (nJ).37. The method according to claim 31, wherein the optical pulse sourcegenerates input optical pulses having a pulse energy of between about1.0 nJ and about 100 nJ.
 38. The method according to claim 31, whereinthe optical pulse source comprises either a mode-locked laser or achirped pulse amplification (CPA) system.
 39. The method according toclaim 38, wherein the mode-locked laser is a mode-locked fiber laser.40. The method according to claim 38, wherein the CPA system is a fiberCPA system.
 41. The method according to claim 31, wherein the opticalpulse source generates input optical pulses such that the firstwavelength is a wavelength within the transparent region of asilica-based fiber.
 42. The method according to claim 41, wherein thefirst wavelength is below 1300 nanometers (nm).
 43. The method accordingto claim 42, wherein the first wavelength is a wavelength between therange of about 300 nm and about 1300 nm.
 44. The method according toclaim 31, wherein the optical pulse source generates input opticalpulses having a subpicosecond pulse width.
 45. The method according toclaim 31, wherein the HOM fiber module produces output optical pulseshaving a pulse energy of at least 1.0 nJ.
 46. The method according toclaim 31, wherein the HOM fiber module produces output optical pulsessuch that the desired wavelength is a wavelength within the transparentregion of a silica-based fiber.
 47. The method according to claim 46,wherein the desired wavelength is below 1300 nm.
 48. The methodaccording to claim 47, wherein the desired wavelength is a wavelengthbetween the range of about 300 nm and about 1300 nm.
 49. The methodaccording to claim 31, wherein the HOM fiber module produces outputoptical pulses having a subpicosecond pulse width.
 50. The methodaccording to claim 32 further comprising: tuning the first wavelength ofthe input optical pulses to an intermediate wavelength prior todelivering the input optical pulses into the HOM fiber.
 51. The methodaccording to claim 50, wherein the tuning comprises subnanosecond powertuning using a power control system connectedly disposed between theoptical pulse source and the HOM fiber module.
 52. The method accordingto claim 51, wherein the power control system is a lithium niobateintensity modulator device.
 53. The method according to claim 32 furthercomprising: varying the length of the HOM fiber so as to vary thedesired wavelength.
 54. The method according to claim 32 furthercomprising: varying the power of the input optical pulses so as to varythe desired wavelength.